NOVEL ISOXAZOLINE AND ISOXAZOLE FIBRINOGEN RECEPTOR ANTAGONISTS

Abstract: This invention relates to novel isoxazolines and isoxazoles which are useful as antagonists of the platelet glycoprotein IIb/IIIa fibrinogen receptor complex, to pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of platelet aggregation, as thrombolytics and/or for the treatment of thromboembolic disorders.

Description: Novel Isoxazoline and Isoxazole Fibrinogen Receptor Antagonists Cross Reference to Earlier Filed Application This application is a continuation-in-part of U.S. Patent Application Serial Number 08/232,961, filed April 22, 1994 which is a continuation-in-part of U.S. Patent Application Serial Number 08/157,598, filed November 24, 1993. The disclosures of these earlier filed applications are hereby incorporated herein by reference. FIELD OF THE INVENTION This invention relates to novel isoxazolines and isoxazoles which are useful as antagonists of the platelet glycoprotein Ilb/IIIa fibrinogen receptor complex, to pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of platelet aggregation, as thrombolytics, and/or for the treatment of thromboembolic disorders. BACKGROUND OF THF, INVENTION Hemostasis is the normal physiological process in which bleeding from an injured blood vessel is arrested. It is a dynamic and complex process in which platelets play a key role. Within seconds of vessel injury, resting platelets become activated and are bound to the exposed matrix of the injured area by a phenomenon called platelet adhesion. Activated platelets also bind to each other in a process called platelet aggregation to form a platelet plug. The platelet plug can stop bleeding quickly, but it must be reinforced by fibrin for long-term effectiveness, until the vessel injury can be permanently repaired. Thrombosis may be regarded as the pathological condition wherein improper activity of the hemostatic mechanism results in intravascular thrombus formation. Activation of platelets and the resulting platelet aggregation and platelet factor secretion has been associated with a variety of pathophysiological conditions including cardiovascular and cerebrovascular thromboembolic disorders, for example, the thromboembolic disorders associated with unstable angina, myocardial infarction, transient ischemic attack, stroke, atherosclerosis and diabetes. The contribution of platelets to these disease processes stems from their ability to form aggregates, or platelet thrombi, especially in the arterial wall following injury. Platelets are activated by a wide variety of agonists resulting in platelet shape change, secretion of granular contents and aggregation. Aggregation of platelets serves to further focus clot formation by concentrating activated clotting factors at the site of injury. Several endogenous agonists including adenosine diphosphate (ADP) , serotonin, arachidonic acid, thrombin, and collagen, have been identified. Because of the involvement of several endogenous agonists in activating platelet function and aggregation, an inhibitor which acts against all agonists would represent a more efficacious antiplatelet agent than currently available antiplatelet drugs, which are agonist-specific. Current antiplatelet drugs are effective against only one type of agonist; these include aspirin, which acts against arachidonic acid; ticlopidine, which acts against ADP; thromboxane A 2 synthetase inhibitors or receptor antagonists, which act against thromboxane A2; and hirudin, which acts against thrombin. Recently, a common pathway for all known agonists has been identified, namely platelet glycoprotein Ilb/IIIa complex (GPIIb/IIIa) , which is the membrane protein mediating platelet aggregation. A recent review of GPIIb/IIIa is provided by Phillips et al. Cell (1991) 65: 359-362. The development of a GPIIb/IIIa antagonist represents a promising new approach for antiplatelet therapy. GPIIb/IIIa does not bind soluble proteins on unstimulated platelets, but GPIIb/IIIa in activated platelets is known to bind four soluble adhesive proteins, namely fibrinogen, von Willebrand factor, fibronectin, and vitronectin. The binding of fibrinogen and von Willebrand factor to GPIIb/IIIa causes platelets to aggregate. The binding of fibrinogen is mediated in part by the Arg-Gly-Asp (RGD) recognition sequence which is common to the adhesive proteins that bind GPIIb/IIIa. In addition to GPIIb/IIIa, increasing numbers of other cell surface receptors have been identified which bind to extracellular matrix ligands or other cell adhesion ligands thereby mediating cell-cell and cell-matrix adhesion processes. These receptors belong to a gene superfamily called integrins and are composed of heterodimeric transmembrane glycoproteins containing α- and β-subunits . Integrin subfamilies contain a common β-subunit combined with different α-subunits to form adhesion receptors with unique specificity. The genes for eight distinct β-subunits have been cloned and sequenced to date. Two members of the βl subfamily, α4/βl and α5/βl have been implicated in various inflammatory processes . Antibodies to α4 prevent adhesion of lymphocytes to synovial endothelial cells in vitro, a process which may be of importance in rheumatoid arthritis (VanDinther- Janssen et al., J. Immunol., 1991, 147:4207) . Additional studies with monoclonal anti-α4 antibodies provide evidence that α4/βl may additionally have a role in allergy, asthma, and autoimmune disorders (Walsh et al., J. Immunol., 1991, 146:3419; Bochner et al. , J. Exp. Med., 1991 173:1553; Yednock et al. , Nature, 1992, 356:63) . Anti-α4 antibodies also block the migration of leukocytes to the site of inflammation (Issedutz et al . , J. Immunol., 1991, 147:4178) . The α v /β3 heterodimer, commonly referred to as the vitronectin receptor, is another member of the ββ integrin subfamily and has been described in platelets, endothelial cells, melanoma, smooth muscle cells and on the surface of osteoclasts (Horton and Davies, J. Bone Min. Res. 1989, 4:803-808; Davies et al. , J. Cell. Biol. 1989, 109:1817-1826; Horton, Int. J. Exp. Pathol . , 1990, 71:741-759) . Like GPIIb/IIIa, the vitronectin receptor binds a variety of RGD-containing adhesive proteins such as vitronectin, fibronectin, VWF, fibrinogen, osteopontin, bone sialo protein II and thrombosponden in a manner mediated by the RGD sequence. Possible roles for o^/β3 in angiogenesis, tumor progression, and neovascularization have been proposed (Brooks et al., Science, 1994, 264:569-571) . A key event in bone resorption is the adhesion of osteoclasts to the matrix of bone. Studies with monoclonal antibodies have implicated the α v /β3 receptor in this process and suggest that a selective θv/β3 antagonist would have utility in blocking bone resorption (Horton et al., J. Bone Miner. Res., 1993, 8:239-247; Helfrich et al., J. Bone Miner. Res., 1992, 7:335-343) . Several RGD-peptidomimetic compounds have been reported which block fibrinogen binding and prevent the formation of platelet thrombi. European Patent Application Publication Number 478363 relates to compounds having the general formula: European Patent Application Publication Number 478328 relates to compounds having the general formula European Patent Application Publication Number 525629 (corresponds to Canadian Patent Application Publication Number 2,074,685) discloses compounds having the general formula: PCT Patent Application 9307867 relates to compounds having the general formula: European Patent Application Publication Number 4512831 relates to compounds having the general formula: R X-(CH 2 ) m -Y-(CH 2 ) k -C-NH-CH-CH-Z O R 1 None of the above references teaches or suggests the compounds of the present invention which are described in detail below. SUMMARY OF THF, INVF.NTION The present invention provides novel nonpeptide compounds which bind to integrin receptors thereby altering cell-matrix and cell-cell adhesion processes . The compounds of the present invention are useful for the treatment of inflammation, bone degradation, tumors, metastases, thrombosis, cell aggregation-related conditions in a mammal. One aspect of this invention provides novel compounds of Formula I (described below) which are useful as antagonists of the platelet glycoprotein Ilb/IIIa complex. The compounds of the present invention inhibit the binding of fibrinogen to platelet glycoprotein Ilb/IIIa complex and inhibit the aggregation of platelets. The present invention also includes pharmaceutical compositions containing such compounds of Formula I, and methods of using such compounds for the inhibition of platelet aggregation, as thrombolytics, and/or for the treatment of thromboembolic disorders. The present invention also includes methods of treating cardiovascular disease, thrombosis or harmful platelet aggregation, reocclusion following thrombolysis, reperfusion injury, or restenosis by administering a compound of Formula I alone or in combination with one or more additional therapeutic agents selected from: anti-coagulants such as warfarin or heparin; anti-platelet agents such as aspirin, piroxicam or ticlopidine; thrombin inhibitors such as boroarginine derivatives, hirudin or argatroban; or thrombolytic agents such as tissue plasminogen activator, anistreplase, urokinase or streptokinase; or combinations thereof. The present invention also provides novel compounds, pharmaceutical compositions and methods which may be used in the treatment or prevention of diseases which involve cell adhesion processes, including, but not limited to, rheumatoid arthritis, asthma, allergies, adult respiratory distress syndrome, graft versus host disease, organ transplantation, septic shock, psoriasis, eczema, contact dermatitis, osteoporosis, osteoarthritis, atherosclerosis, metastasis, wound healing, diabetic retinopathy, inflammatory bowel disease and other autoimmune diseases. Also included in the present invention are pharmaceutical kits comprising one or more containers containing pharmaceutical dosage units comprising a compound of Formula I, for the treatment of cell adhesion related disorders, including but not limited to thromboembolic disorders. DETAILED DESCRIPTION QF THE INVENTION The present invention provides novel nonpeptide compounds of Formula I (described below) which bind to integrin receptors thereby altering cell-matrix and cell-cell adhesion processes. The compounds of the present invention are useful for the treatment of inflammation, bone degradation, tumors, metastases, thrombosis, cell aggregation-related conditions in a mammal. One aspect of this invention provides compounds of Formula I (described below) which are useful as antagonists of the platelet glycoprotein Ilb/IIIa complex. The compounds of the present invention inhibit the binding of fibrinogen to the platelet glycoprotein Ilb/IIIa complex and inhibit the aggregation of platelets. The present invention also includes pharmaceutical compositions containing such compounds of Formula I, and methods of using such compounds for the inhibition of platelet aggregation, as thrombolytics, and/or for the treatment of thromboembolic disorders . This invention relates to novel compounds of the Formula I : or a pharmaceutically acceptable salt or prodrug form thereof. [1] A first embodiment of this invention provides compounds of Formula I: or pharmaceutically acceptable salt or prodrug forms thereof wherein: b is a single or double bond; R 1 is selected from R 2 (R 3 )N(CH 2 ) q Z-, R 2 (R 3 )N(R 2 N=)CN(R 2 ) (CH 2 ) q Z-, piperazinyl- (CH 2 ) q Z- or Z is selected from O, S, S(=0) , or S(=0) 2 ; R 2 and R 3 are independently selected from: H, Cχ-Cιo alkyl, C 2 -C 6 alkenyl, C3-C 11 cycloalkyl, C 4 -C 11 cycloalkylalkyl, C6~Cιo aryl, C 7 -C 3.1 arylalkyl, C2-C7 alkylcarbonyl, Cε-Cio arylcarbonyl, C2-C 1 0 alkoxycarbonyl, C 4 -C 11 cycloalkoxycarbonyl, C 7 -C 11 bicycloalkoxycarbonyl, C6-C 1 0 aryloxycarbonyl, aryl(Cι-Cιo alkoxy) carbonyl, Ci-Cβ alkylcarbonyloxy(C 1 -C 4 alkoxy) carbonyl, Cβ-Cio arylcarbonyloxy(C 1 -C 4 alkoxy) carbonyl, C 4 -C 11 cycloalkylcarbonyloxy(C 1 -C 4 alkoxy) carbonyl; U is selected from: a single bond (i.e., U is not present), -(C 1 -C 7 alkyl)-, -(C2-C 7 alkenyl)-, -(C 2 -C 7 alkynyl)-, -(aryl)- substituted with 0-3 R 6a , or -(pyridyl)- substituted with 0-3 R 6a ; V is selected from: a single bond (i.e., V is not present); -(C 1 -C 7 alkyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; -(C 2 -C 7 alkenyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; -(C 2 -C 7 alkynyl)-, substituted with 0-2 groups independently selected from R 6 or R 7 ; -(aryl)-, substituted with 0-2 groups independently selected from R 6 or R 7 ; -(pyridyl)-, substituted with 0-2 groups independently selected from R 6 or R 7 ; or - (pyridazinyl)-, substituted with 0-2 groups independently selected from R 6 or R 7 ; W is selected from: a single bond (i.e., W is not present), -(C 1 -C 7 alkyl)-, -(C 2 -C 7 alkenyl)-, -(C 2 -C 7 alkynyl)-, or X is selected from: a single bond (i.e., X is not present); -(C 1 -C 7 alkyl)-, substituted with 0-3 groups independently selected from R 4 , R 8 or R 14 ; -(C2-C 7 alkenyl)-, substituted with 0-3 groups independently selected from R 4 , R 8 or R 14 ; -(C 2 -C 7 alkynyl)-, substituted with 0-2 groups independently selected from R 4 , R 8 or R 14 ; or Y is selected from hydroxy, Ci to Cio alkyloxy, C3 to C 11 cycloalkyloxy, CQ to Cio aryloxy, C 7 to Cχι aralkyloxy, C3 to Cio alkylcarbonyloxyalkyloxy, C3 to Cio alkoxycarbonyloxyalkyloxy, C 2 to Cio alkoxycarbonylalkyloxy, C 5 to Cio cycloalkylcarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonyloxyalkyloxy, C5 to Cio cycloalkoxycarbonylalkyloxy, C 7 to Cu aryloxycarbonylalkyloxy, Cβ to C 12 aryloxycarbonyloxyalkyloxy, Cs to C 12 arylcarbonyloxyalkyloxy, C 5 to C o alkoxyalkylcarbonyloxyalkyloxy, C 5 to Cio (5-alkyl- 1,3-dioxa-cycloρenten-2-one-yl)methyloxy, Cio to C 14 (5-aryl-l,3-dioxa-cyclopenten-2-one-yl)methyloxy; or (R 2 ) (R 3 )N-(Cι-Cιo alkoxy)-; R 4 and R b are independently selected from H, C 1 -C 10 alkyl, hydroxy, C 1 -C 10 alkoxy, nitro, C 1 -C 10 alkylcarbonyl, or -N(R 12 )R 13 ; ' R 5 is selected from H, Ci-Cβ alkyl, C 2 -C6 alkenyl, C3-C11 cycloalkyl, C 4 -C 11 cycloalkylmethyl, Cε-Cio aryl, C 7 -C 11 arylalkyl, or C 1 -C 1 0 alkyl substituted with 0-2 R 4b ; R 5a is selected from hydrogen, hydroxy, Ci to Cβ alkyl, C 2 to CQ alkenyl, C3 to Cu cycloalkyl, C 4 to Cn cycloalkylmethyl, Ci-Cβ alkoxy, benzyloxy, Cβ to Cio aryl, heteroaryl, heteroarylalkyl, C 7 to Cn arylalkyl, adamantylmethyl or C 1 -C 1 0 alkyl substituted with 0-2 R 4b ; alternately, R 5 and R 5a can be taken together to be 3- azabicyclononyl, 1-piperidinyl, 1-morpholinyl or 1- piperazinyl, each being optionally substituted with Ci-Cβ alkyl, C6-C 1 0 aryl, heteroaryl, C 7 -C 11 arylalkyl, Ci-Cβ alkylcarbonyl, C3-C 7 cycloalkylcarbonyl, C 1 -C 6 alkoxycarbonyl, C 7 -C 11 arylalkoxycarbonyl, Ci-Cβ alkylsulfonyl or Cβ-Cio arylsulfonyl; R 5b is selected from Ci-Cβ alkyl, C2-C6 alkenyl, C3-C 11 cycloalkyl, C 4 -C 11 cycloalkylmethyl, C6-C 1 0 aryl, C 7 -C 11 arylalkyl, or C 1 -C 1 0 alkyl substituted with 0-2 R 4b ; R 6 is selected from H, C 1 -C 1 0 alkyl, hydroxy, C 1 -C 1 0 alkoxy, nitro, C 1 -C 1 0 alkylcarbonyl, -N(R 12 )R 13 , cyano, halo, CF3, CHO, CO 2 R 5 , C(=0)R 5a , CONR 5 R 5a , 0C(=0)R 5a , OC(=0)OR 5b , OR 5a , OC (=0)NR 5 R 5a , OCH 2 CO2R 5 , CO 2 CH 2 CO 2 R 5 , NO 2 , NR 5a C(=0)R 5a , NR 5a C(=0)0R 5b , NR 5a C(=0)NR 5 R 5a , NR 5a Sθ 2 NR 5 R 5a , NR 5a S0 2 R 5 , S(0) p R 5a , Sθ 2 NR 5 R 5a , C2 to C6 alkenyl, C3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl; C δ to Cio aryl optionally substituted with 1-3 groups selected from halogen, C 1 -C6 alkoxy, Ci-Cβ alkyl, CF3, S(0)mMe, or -NMe2; C 7 to Cn arylalkyl, said aryl being optionally substituted with 1-3 groups selected from halogen, C 1 -C6 alkoxy, Ci-Cβ alkyl, CF3, S(0)mMe, or -NMe 2 ; methylenedioxy when R 6 is a substituent on aryl; or a 5-10 membered heterocyclic ring containing 1-3 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R 7 ; R 6a is selected from C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halo, CF3, NO 2 , or NR 12 R 13 ; R 7 is selected from H, C 1 -C 1 0 alkyl, hydroxy, C 1 -C 1 0 alkoxy, nitro, C 1 -C 1 0 alkylcarbonyl, -N(R 12 )R 13 , cyano, halo, CF3, CHO, CO2R 5 , C(=0)R 5a , C0NR 5 R 5a , 0C(=0)R 5a , 0C(=0)0R 5b , 0R 5a , OC(=0)NR 5 R 5a , OCH 2 CO 2 R 5 , CO 2 CH 2 CO 2 R 5 , Nθ 2 , NR 5a C(=0)R 5a , NR 5a C(=0)0R 5b , NR 5a C(=0)NR 5 R 5a , NR 5a S0 2 NR 5 R 5a , NR 5a S0 2 R 5 , S(0) p R 5a , S0 2 NR 5 R 5a , C 2 to C6 alkenyl, C 3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl, Cβ to Cio aryl, or C7 to Cn arylalkyl; R 8 is selected from: H; R 6 ; i-Cio alkyl, substituted with 0-3 R 6 ; C 2 -C 10 alkenyl, substituted with 0-3 R 6 ; C 2 -C 10 alkynyl, substituted with 0-3 R 6 ; C3-C8 cycloalkyl, substituted with 0-3 R 6 ; C5-C6 cycloalkenyl, substituted with 0-2 R 6 ; aryl, substituted with 0-2 R 6 ; 5-10 membered heterocyclic ring containing 1-3 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R 6 ; R 12 and R 13 are independently H, C 1 -C 1 0 alkyl, C1-C10 alkoxycarbonyl, C 1 -C 1 0 alkylcarbonyl, C 1 -C 1 0 alkylsulfonyl, aryl (C 1 -C 1 0 alkyl) sulfonyl, arylsulfonyl, aryl, C2-C6 alkenyl, C3-C 11 cycloalkyl, C 4 -C 11 cycloalkylalkyl, C 7 -C 11 arylalkyl, C2-C 7 alkylcarbonyl, C 7 -C 11 arylcarbonyl, C 2 -C 1 0 alkoxycarbonyl, C 4 -C 11 cycloalkoxycarbonyl, C 7 -C 11 bicycloalkoxycarbonyl, C 7 -C 11 aryloxycarbonyl, heteroarylcarbonyl, heteroarylalkylcarbonyl or aryl (C1-C 1 0 alkoxy)carbonyl; R 14 is selected from H, C 1 -C 1 0 alkyl, C 2 -C 1 0 alkenyl, 2~ ιo alkynyl, C 1 -C 1 0 alkoxy, aryl, heteroaryl or C 1 -C 1 0 alkoxycarbonyl, CO 2 R 5 or -C (=0)N(R 5 )R 5a ; R 15 is selected from: H; R 6 ; C 1 -C 1 0 alkyl, substituted with 0-8 R 6 ; C 2 -C 1 0 alkenyl, substituted with 0-6 R 6 ; C 1 -C 1 0 alkoxy, substituted with 0-6 R 6 ; aryl, substituted with 0-5 R 6 ; 5-6 membered heterocyclic ring containing 1-2 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-5 R 6 ; Ci-Cio alkoxycarbonyl substituted with 0-8 R 6 ; CO2R 5 ; or -C(=0)N(R 5 )R 5a ; provided that when b is a double bond, only one of R 14 or R 15 is present; provided that n, q, and r are chosen such that the number of in-chain atoms between R 1 and Y is in the range of 8-18. [2] Preferred compounds of this first embodiment are those of Formula II (where W is a single bond (i.e., absent) and U is a single bond (i.e., absent)) : wherein; R 1 is selected from R 2 HN(CH 2 ) q O-, R 2 HN(R 2 N=)CNH(CH 2 )qO-, piperazinyl- (CH 2 ) q O-, or R 2 is selected from H, aryl (Ci-Cio alkoxy)carbonyl, Ci-Cio alkoxycarbonyl; and/or R 8 is selected from H, Ci-Cio alkyl, C 2 -C 1 0 alkenyl, C 3 -C 8 cycloalkyl, C 5 -C6 cycloalkenyl, aryl, 5-6 membered heterocyclic ring containing 1-2 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated; and/or R 6 and R 7 are selected from H, C 1 -C 10 alkyl, hydroxy, 1 -C 1 0 alkoxy, nitro, C 1 -C 1 0 alkylcarbonyl, -N(R 12 )R 13 , cyano, or halo. [3] Further preferred compounds of this first embodiment are those of Formula II (where W is a bond/absent and U is a bond/absent) : wherein: X is selected from: a single bond (i.e., X is not present); -(C 1 -C 7 alkyl)-, substituted with 0-2 groups independently selected from R 4 , R 8 or R 14 ; -(C 2 -C 7 alkenyl)-, substituted with 0-2 groups independently selected from R 4 , R 8 or R 14 ; -(C 2 -C 7 alkynyl)-, substituted with 0-2 groups independently selected from R 4 , R 8 or R 14 ; and/or R 8 is selected from H, C 1 -C6 alkyl, C 2 -C6 alkenyl, C3-C 8 cycloalkyl, C 5 -C6 cycloalkenyl, aryl, 5-6 membered heterocyclic ring containing 1-2 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated. [4] Further preferred compounds of this first embodiment are compounds of Formula I wherein: R 1 is V is phenylene or pyridylene; n is 1 or 2; X is -(C 1 -C 2 ) alkyl- substituted with 0-2 R 4 Y is selected from: hydroxy; Ci to Cio alkoxy; methylcarbonyloxymethoxy-; ethylcarbonyloxymethoxy-; t-butylcarbonyloxymethoxy-; cyclohexylcarbonyloxymethoxy-; 1- (methylcarbonyloxy)ethoxy-; 1- (ethylcarbonyloxy)ethoxy-; 1- (t-butylcarbonyloxy) ethoxy-; 1- (cyclohexylcarbonyloxy)ethoxy-; i-propyloxycarbonyloxymethoxy-; t-butyloxycarbonyloxymethoxy-; 1- (i-propyloxycarbonyloxy)ethoxy-; 1- (cyclohexyloxycarbonyloxy) ethoxy-; 1- (t-butyloxycarbonyloxy) ethoxy-; dimethylaminoethoxy-; diethylaminoethoxy-; (5-methyl-l,3-dioxacyclopenten-2-on-4-yl)methoxy-; (5- (t-butyl)-1,3-dioxacyclopenten-2-on-4- y1)methoxy-; (1,3-dioxa-5-phenyl-cyclopenten-2-on-4-yl)methoxy-; 1- (2- (2-methoxypropyl) carbonyloxy) ethoxy-; R 4 is -NR 12 R 13 ; R 12 is H, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyl, Cι~ C 4 alkylsulfonyl, arylalkylsulfonyl, arylsulfonyl, benzyl, benzoyl, phenoxycarbonyl, benzyloxycarbonyl, arylalkylsulfonyl, pyridylcarbonyl, or pyridylmethylcarbonyl; R 13 is H. [5] Specifically preferred compounds of this first embodiment are compounds, or pharmaceutically acceptable salt or prodrug forms thereof, selected from: 5 (R. S)-3-[ [4- (2-piperidin-4-yl)ethoxyphenyl] isoxazolin- 5-yl]acetic acid; 5 (R, S) -N-(butanesulfonyl)-L-{3-[4-(2-piperidin-4- yl)ethoxyphenyl] isoxazolin-5-ylJglycine; 5 (JR, S) -N- (α-toluenesulfonyl)-L-{3- [4- (2-piperidin-4- yl)ethoxyphenyl] isoxazolin-5-yl}glycine; 5 (R, S) -N- [ (benzyloxy)carbonyl]- -{3- [4- (2-piperidin-4- yl)ethoxyphenyl] isoxazolin-5-yl}glycine; 5 (R, S) -N- (pentanoyl)-L-{3- [4- (2-piperidin-4-yl)ethox¬ yphenyl] isoxazolin-5-yl}glycine; 5 (R, S)-3-{ [4-(piperidin-4-yl)methoxyphenyl] isoxazolin-5- yljpropanoic acid; 2 (R, S) - (R, S) -N- (butanesulfonyl)amino-{3- [4- (piperidin- 4-yl)methoxyphenyl]isoxazolin-5-ylIpropanoic acid; 2 (R, S) -S (R f S) -N- (α-toluenesulfonyl) amino-{3- [4- (piperi- din-4-yl)methoxyphenyl] isoxazolin-5-ylJpropanoic acid; 2 (R,5)-5 (R, S) -N- [ (benzyloxy) carbonyl]amino-{3- [4- (piper¬ idin-4-yl)methoxyphenyl] isoxazolin-5-ylJpropanoic acid; 2 (R, S) -5 (R, S) -N- (pentanoyl)amino-{3- [4- (piperidin-4- yl)methoxyphenyl] isoxazolin-5-ylIpropanoic acid. [6] A second embodiment of this invention provides a compound of Formula I: or a pharmaceutically acceptable salt or prodrug form thereof wherein: b is a single or double bond; R 1 is selected from R 2a (R 3 )N-, R 2 (R 3 )N(R 2 N=) C-, R 2a (R 3) N (CH 2 ) q Z-, R 2 (R 3 )N(R 2 N=) C(CH 2 ) q Z-, R 2 (R 3 )N(R 2 N=)CN(R 2 )-, Z is selected from a bond (i.e. is absent), 0, S, S (=0) , S(=0) 2 ; R 2 and R 3 are independently selected from: H, Ci-Cio alkyl, C3-C6 alkenyl, C3-C 11 cycloalkyl, C 4 -C 11 cycloalkylalkyl, Cβ-Cio aryl, C 7 -C 11 ary l a lk y l , C2-C 7 alkylcarbonyl, C 7 -C 11 arylcarbonyl, C2-C 1 0 alkoxycarbonyl, C 4 -C 11 cycloalkoxycarbonyl, C 7 -C 11 bicycloalkoxycarbonyl, C 7 -C 11 aryloxycarbonyl, aryl (C1-C10 alkoxy)carbonyl, Ci-Cβ alkylcarbonylox (C 1 -C 4 alkoxy) carbonyl, Cβ-Cio arylcarbonyloxy(C 1 -C 4 alkoxy) carbonyl, C 4 -C 11 cycloalkylcarbonyloxy(C 1 -C 4 alkoxy)carbonyl; ; R 2a i s R 2 or R 2 (R 3 )N(R 2 N=)C _ ; U is selected from: a single bond (i.e., U is not present), -(C 1 -C 7 alkyl)-, -(C2-C 7 alkenyl)-, -(C2-C7 alkynyl)-, -(aryl)- substituted with 0-3 R 6a , or -(pyridyl)- substituted with 0-3 R 6a ; V is selected from: a single bond (i.e., V is not present); -(C 1 -C 7 alkyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; -(C 2 -C 7 alkenyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; -(C 2 -C 7 alkynyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; - (phenyl)-Q-, said phenyl substituted with 0-2 groups independently selected from R 6 or R 7 ; - (pyridyl)-Q-, said pyridyl substituted with 0-2 groups independently selected from R 6 or R 7 ; or - (pyridazinyl) -Q-, said pyridazinyl substituted with 0-2 groups independently selected from R 6 or R 7 ' Q is selected from: a single bond (i.e., Q is not present), -0-, -S(0) m -, -N(R 12 )-, -(CH 2 )m-, ~C(=0)-, -N(R 5a )C(=0)-, -C(=0)N(R 5a )-, -CH 2 0-, -OCH2-, -CH 2 N(R 12 )-, -N(R 12 )CH 2 -, -CH 2 C(=0)-, -C(=0)CH 2 -, -CH 2 S(0) m -, or -S(0) m CH 2 -, provided that when b is a single bond, and R 1 -U-V- is a substituent on C5 of the central 5-membered ring of Formula I, then Q is not -0-, -S(0) m -, -N(R 12 )-, -C(=0)N(R 5a )-, -CH 2 0-, CH 2 N(R 12 )- or -CH 2 S(0) m -; W is selected from: -C (=0)-N(R 5a )- (C (R 4 )2)n-; X is selected from: a single bond (i.e. X is absent) ~(C(R ) 2 )n-C(R 4 ) (R 8 )-C(R 4 ) (R 4a )-, with the proviso that when n is 0 or 1, then at least one of R 4a or R 8 is other than H or methyl; Y is selected from hydroxy, Ci to Cio alkyloxy, C3 to Cn cycloalkyloxy, Cβ to Cio aryloxy, C 7 to Cn aralkyloxy, C3 to Cio alkylcarbonyloxyalkyloxy, C 3 to Cio alkoxycarbonyloxyalkyloxy, C 2 to Cio alkoxycarbonylalkyloxy, C 5 to Cio cycloalkylcarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonylalkyloxy, C 7 to Cn aryloxycarbonylalkyloxy, Cβ to C 12 aryloxycarbonyloxyalkyloxy, Cβ to C 12 arylcarbonyloxyalkyloxy, C 5 to Cio alkoxyalkylcarbonyloxyalkyloxy, C 5 to Cio (5-alkyl- 1,3-dioxa-cyclopenten-2-one-yl)methyloxy, Cio to C 14 (5-aryl-l,3-dioxa-cyclopenten-2-one-yl)methyloxy, (R 2 ) (R 3 )N-(Cι-Cιo alkoxy)-; R 4 is selected from H, C 1 -C 1 0 alkyl, C 1 -C 1 0 alkylcarbonyl, aryl, arylalkyl, cycloalkyl, or cycloalkylalkyl; alternately, two R 4 groups on adjacent carbons may join to form a bond (i.e. a carbon-carbon double or triple bond) ; R 4a is selected from H, hydroxy, C 1 -C 1 0 alkoxy, nitro, N(R 5 )R 5a , -N(R 12 )R 13 , -N(R 16 )R 17 , C 1 -C 1 0 alkyl substituted with 0-3 R 6 , aryl substituted with 0-3 R 6 , heteroaryl substituted with 0-3 R 6 or C 1 -C 1 0 alkylcarbonyl; R 4b is selected from H, C 1 -C6 alkyl, C 2 -C 6 alkenyl, C2- Cβ alkynyl, C3-C 7 cycloalkyl, C 7 -C 14 bicycloalkyl, hydroxy, Ci-Cβ alkoxy, Ci-C δ alkylthio, Ci-Cβ alkylsulfinyl, C 1 -C 6 alkylsulfonyl, nitro, Ci-C δ alkylcarbonyl, Cβ-Cio aryl, -N(R 12 )R 13 ; halo, CF3, CN, Ci-Cβ alkoxycarbonyl, carboxy, piperidinyl, morpholinyl or pyridinyl; R 5 is selected from H, Cι~Cβ alkyl, C3-C6 alkenyl, C3-C 11 cycloalkyl, C 4 -C 11 cycloalkylmethyl, C6-C 1 0 aryl, C 7 -C 11 arylalkyl, or C 1 -C 1 0 alkyl substituted with 0-2 R b ; R 5a is selected from hydrogen, hydroxy, Ci to Cβ alkyl, C3-C 6 alkenyl, C3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl, Ci-Cβ alkoxy, benzyloxy, C to Cio aryl, heteroaryl, heteroarylalkyl, C 7 to Cn arylalkyl, adamantylmethyl, or C 1 -C 1 0 alkyl substituted with 0-2 R b ; alternately, R 5 and R 5a when both are substituents on the same nitrogen atom (as in -NR 5 R 5a ) can be taken together with the nitrogen atom to which they are attached to form 3-azabicyclononyl, 1,2,3,4- tetrahydro-1-quinolinyl, 1,2, 3, -tetrahydro-2- isoquinolinyl, 1-piperidinyl, 1-morpholinyl, 1- pyrrolidinyl, thiamorpholinyl, thiazolidinyl or 1- piperazinyl, each being optionally substituted with C 1 -C6 alkyl, C6-C 1 0 aryl, heteroaryl, C 7 -C 11 arylalkyl, Ci-Cβ alkylcarbonyl, C3-C 7 cycloalkylcarbonyl, Ci-Cβ alkoxycarbonyl, C 7 -C 11 arylalkoxycarbonyl, Ci-Cβ alkylsulfonyl or C6-C 10 arylsulfonyl; R 5b is selected from Ci-Cβ alkyl, C 2 -C6 alkenyl, C3-C11 cycloalkyl, C 4 -C 11 cycloalkylmethyl, Cβ-Cio aryl, C 7 -C 11 arylalkyl, or C 1 -C 1 0 alkyl substituted with 0-2 R 4b ; R 6 is selected from H, C 1 -C 1 0 alkyl, hydroxy, C 1 -C 1 0 alkoxy, nitro, C 1 -C 1 0 alkylcarbonyl, -N(R 12 )R 13 , cyano, halo, CF3, CHO, CO2R 5 , C(=0)R 5a , CONR 5 R 5a , OC(=0)R 5a , OC(=0)OR 5b , OR 5a , OC(=0)NR 5 R 5a , OCH 2 CO 2 R 5 , CO 2 CH 2 CO 2 R 5 , NO 2 , NR 5a C(=0)R 5a , NR 5a C(=0)OR 5b , NR 5a C(=0)NR 5 R 5a , NR 5a S02NR 5 R 5a , NR 5a S02R 5 , S(0) m R 5a , Sθ 2 NR 5 R 5a , SiMe3, C 2 to Cε alkenyl, C3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl; Cβ to Cio aryl optionally substituted with 1-3 groups selected from halogen, C 1 -C6 alkoxy, C 1 -C6 alkyl, CF3, S(0) m Me, or -NMe 2 ; C 7 to Cn arylalkyl, said aryl being optionally substituted with 1-3 groups selected from halogen, C1-C6 alkoxy, Ci-Cέ alkyl, CF3, S(0) m Me, or -NMe 2 ; methylenedioxy when R^ is a substituent on aryl; or a 5-10 membered heterocyclic ring containing 1-3 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R 7 ; R 6a is selected from C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halo, CF 3 , NO2, or NR 12 R 13 ; R 7 is selected from H, C 1 -C 1 0 alkyl, hydroxy, C 1 -C 1 0 alkoxy, nitro, C 1 -C 10 alkylcarbonyl, -N(R 12 )R 13 , cyano, halo, CF 3 , CHO, CO 2 R 5 , C(=0)R 5a , CONR 5 R 5a , OC(=0)R 5a , OC(=0)OR 5b , 0R 5a , OC(=0)NR 5 R 5a , OCH2CO2R 5 , CO2CH 2 CO 2 R 5 , NO2, NR 5a C(=0)R 5a , NR 5a C(=0)OR 5b , NR 5a C(=0)NR 5 R 5a , NR 5a S0 2 NR 5 R 5a , NR 5a S0 2 R 5 , S(0) m R 5a , S0 2 NR 5 R 5a , C 2 to C 6 alkenyl, C3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl, Cg to Cio aryl, or C 7 to Cn arylalkyl; R 8 is selected from: R 6 ; C 1 -C 1 0 alkyl, substituted with 0-3 R 6 ; C 2 -C 10 alkenyl, substituted with 0-3 R 6 ; 2-C 1 0 alkynyl, substituted with 0-3 R 6 ; C3-C8 cycloalkyl, substituted with 0-3 R 6 ; C 5 -C6 cycloalkenyl, substituted with 0-3 R 6 ; aryl, substituted with 0-3 R 6 ; 5-10 membered heterocyclic ring containing 1-3 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R 6 ; R 12 and R 13 are independently H, C 1 -C 1 0 alkyl, C1-C1 0 alkoxycarbonyl, C 1 -C 1 0 alkylcarbonyl, C 1 -C 10 alkylsulfonyl, aryl(Cι~Cιo alkyl) sulfonyl, arylsulfonyl, aryl(C2~Cιo alkenyl) sulfonyl, heteroarylsulfonyl, aryl, C 2 -C6 alkenyl, C3-C 11 cycloalkyl, C 4 -C 11 cycloalkylalkyl, C 7 -C 11 arylalkyl, C 7 -C 11 arylcarbonyl, C 4 -C 11 cycloalkoxycarbonyl, C 7 -C 11 bicycloalkoxycarbonyl, C 7 -C 11 aryloxycarbonyl, heteroarylcarbonyl, heteroarylalkylcarbonyl, or aryl (C 1 -C 1 0 alkoxy) carbonyl, wherein said aryls are optionally substituted with 0-3 substituents selected from the group consisting of: C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halo, CF 3 , and NO 2 ; R 14 is selected from H, C 1 -C 1 0 alkyl, C 2 -C 1 0 alkenyl, C2-C 1 0 alkynyl, C 1 -C 1 0 alkoxy, aryl, heteroaryl or Cι-C- 1 0 alkoxycarbonyl, CO 2 R 5 or -C (=0)N(R 5 )R 5a ; R 15 is selected from: H; R 6 ; -CO 2 R 5 ; -C (=0)N(R 5 )R 5a ; C 1 -C 1 0 alkoxycarbonyl substituted with 0-2 R 6 ; C 1 -C 1 0 alkyl, substituted with 0-3 R 6 ; C 2 -C 10 alkenyl, substituted with 0-3 R 6 ; C 1 -C 1 0 alkoxy, substituted with 0-3 R 6 ; aryl, substituted with 0-3 R 6 ; or 5-10 membered heterocyclic ring containing 1-3 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R 6 ; provided that when b is a double bond, only one of R 14 or R 15 is present; R 16 is selected from: -C(=0)-0-R 18a , -C(=0)-R 18b , -C(=0)N(R 18b ) 2 , -C(=0)NHSθ2R l8a , -C(=0)NHC(=0)R 18b , -C(=0)NHC(=0)OR 18a , -C(=0)NHS0 2 NHR 18b , -C(=S)-NH-R 18b , -NH-C(=0)-0-R 18a , -NH-C(=0)-R 18b , -NH-C(=0)-NH-R 18b , -S0 2 -0-R 18a , -Sθ2-R 18a , -S0 2 -N ( 18 b ) 2 , -S02-NHC (=0) 018 b , -P (=S ) (OR 18a ) 2 , -P (=0) (0R 18a ) 2 , -P (=S) (R 18a ) 2 , -P (=0) (R 18a ) 2 , or R 17 is selected from: H, Ci-Cio alkyl, C 2 -C6 alkenyl, C3- C 11 cycloalkyl, C 4 -C 15 cycloalkylalkyl, aryl, aryl(Cι-Cio alkyl)-; R 18a is selected from: Ci-Cβ alkyl substituted with 0-2 R 19 , C 2 -C 8 alkenyl substituted with 0-2 R 19 , C 2 -C8 alkynyl substituted with 0-2 R 19 , C3-C8 cycloalkyl substituted with 0-2 R 19 , aryl substituted with 0-4 R 19 , aryl (C 1 -C6 alkyl)- substituted with 0-4 R 19 , a 5-10 membered heterocyclic ring system having 1-3 heteroatoms selected independently from 0, S, and N, said heterocyclic ring being substituted with 0-4 R 19 , Ci-Cβ alkyl substituted with a 5-10 membered heterocyclic ring system having 1-3 heteroatoms selected independently from 0, S, and N, said heterocyclic ring being substituted with 0-4 R 19 ; l8b i s selected from R 18a or H; R 19 is selected from H, halogen, CF3, CN, NO 2 , NR 12 R 13 , Ci-Cβ alkyl, C 2 -C6 alkenyl, C 2 -C6 alkynyl, C3-C11 cycloalkyl, C 4 -C 11 cycloalkylalkyl, aryl, aryl (C1-C6 alkyl)-, C 1 -C 6 alkoxy, or C 1 -C 4 alkoxycarbonyl; provided that n, q and r are chosen such that the number of atoms connecting R 1 and Y is in the range of 8-18. [7] Preferred compounds of this second embodiment are those compounds of Formula la: wherein: Z is selected from a bond (i.e. is absent), 0, or S; and/or R 2 is selected from H, aryl(Cι-Cιo alkoxy) carbonyl, or 1 -C 1 0 alkoxycarbonyl; and/or W is -(CH2) n C(=0)N(R 5a )-; and/or X is -(C(R )2) n -C(R 4 ) (R 8 )-CH(R 4 )-, with the proviso that when n is 0 or 1, then at least one of R a or R 8 is other than H or methyl; and/or R 5 is selected from H or C 1 -C 1 0 alkyl substituted with 0-6 R 4b ; and/or R 6 is selected from H, Ci-Cio alkyl, hydroxy, Ci-Cio alkoxy, nitro, Ci-Cio alkylcarbonyl, -N(R 12 )R 13 , -NR 5 R 5a , C0 2 R 5 , S(0) m R 5 , OR 5 , cyano, halo; Cβ to Cio aryl optionally substituted with 1-3 groups selected from halogen, Ci-Cβ alkoxy, Cι~ alkyl, CF3, S(0)mMe, or -NMe 2 ; C 7 to Cn arylalkyl, said aryl being optionally substituted with 1-3 groups selected from halogen, C 1 -C6 alkoxy, Ci-Cg alkyl, CF 3 , S(0) m Me, or -NMe 2 ; methylenedioxy when R> is a substituent on aryl; or a 5-10 membered heterocyclic ring containing 1-3 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R 7 ; and/or R 7 is selected from selected from H, C 1 -C 10 alkyl, hydroxy, C 1 -C 10 alkoxy, nitro, C 1 -C 1 0 alkylcarbonyl, -N(R 12 )R 13 , cyano, or halo; and/or R 8 is selected from: -CONR 5 NR 5a ; -CO2R 5 ; C 1 -C 1 0 alkyl, substituted with 0-3 R 6 ; C 2 -C 10 alkenyl, substituted with 0-3 R 6 ; C 2 -C 1 0 alkynyl, substituted with 0-3 R 6 , C3-C8 cycloalkyl, substituted with 0-3 R 6 ; C 5 -C6 cycloalkenyl, substituted with 0-3 R 6 ; aryl, substituted with 0-2 R 6 ; 5-10 membered heterocyclic ring containing 1-3 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R 6 ; and/or R 12 and R 13 are each independently selected from H, Ci-Cio alkyl, Cι~Cιo alkoxycarbonyl, Cι~Cιo alkylcarbonyl, Cι~Cιo alkylsulfonyl, aryl(Cι-Cιo alkyl) sulfonyl, arylsulfonyl, aryl, heteroarylcarbonyl, or heteroarylalkylcarbonyl, wherein said aryls are optionally substituted with 0-3 substituents selected from the group consisting of: C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halo, CF3, and NO 2 . [8] Further preferred compounds of this second embodiment are those compounds of Formula la: wherein: Z is selected from a bond (i.e. is absent) or O; and/or W is -(CH 2 ) n C(=0)N(R 12 )-; and/or X is -C(R 4 ) (R 8 )-C(R 4 ) 2 -. [9] Further preferred compounds of this second embodiment are compounds of Formula la, wherein: R 1 is R 2 NHC(=NR 2 )- or R 2 NHC(=NR 2 )NH- and V is phenylene or pyridylene, or R 1 iis and V is a single bond (i.e. V n is 1 or 2; X is -CHR 8 CH 2 -; is selected from: hydroxy; Ci to Cio alkoxy; methylcarbonyloxymethoxy-; ethylcarbonyloxymethoxy-; t-butylcarbonyloxymethoxy-; cyclohexylcarbonyloxymethoxy-; 1- (methylcarbonyloxy)ethoxy-; 1-(ethylcarbonyloxy)ethoxy-; 1- (t-butylcarbonyloxy) ethoxy-; 1- (cyclohexylcarbonyloxy)ethoxy-; i-propyloxycarbonyloxymethoxy-; t-butyloxycarbonyloxymethoxy-; 1- (i-propyloxycarbonyloxy)ethoxy-; 1- (cyclohexyloxycarbonyloxy)ethoxy-; 1- (t-butyloxycarbonyloxy)ethoxy-; dimethylaminoethoxy-; diethylaminoethoxy-; (5-methyl-l,3-dioxacyclopenten-2-on-4-yl)methoxy-; (5- ( t-butyl) -1, 3-dioxacyclopenten-2-on-4- yl) methoxy-; (1 , 3-dioxa-5-phenyl-cyclopenten-2-on-4-yl) methoxy-; 1- (2- (2-methoxypropyl) carbonyloxy) ethoxy- ; R 6 is selected from H, C 1 -C 4 alkyl, hydroxy, C 1 -C 4 alkoxy, nitro, C 1 -C 1 0 alkylcarbonyl, -N(R 12 )R 13 , -NR 5 R 5a , CO 2 R 5 , S(0) m R 5 , OR 5 , cyano, halo; C δ to Cio aryl optionally substituted with 1-3 groups selected from halogen, C 1 -C6 alkoxy, Cι~Cβ alkyl, CF 3 , S(0)mMe, or -NMe 2 ; methylenedioxy when R 6 is a substituent on aryl; or a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, triazolyl, imidazolyl, benzofuranyl, indolyl, indolinyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyridinyl, 3H- indolyl, carbazolyl, pyrrolidinyl, piperidinyl, indolinyl, isoxazolinyl or morpholinyl; R 8 is selected from: -C0NR 5 NR 5a ; -CO2R 5 ; C 1 -C 1 0 alkyl, substituted with 0-3 R 6 ; C2-C 1 0 alkenyl, substituted with 0-3 R 6 ; C2-C 1 0 alkynyl, substituted with 0-3 R 6 , C3-C8 cycloalkyl, substituted with 0-3 R 6 ; aryl, substituted with 0-2 R 6 ; a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, triazolyl, imidazolyl, benzofuranyl, indolyl, indolinyl, quinolinyl, isoquinolinyl, isoxazolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyridinyl, 3H-indolyl, carbazolyl, pyrrolidinyl, piperidinyl, indolinyl, or morpholinyl, said heterocyclic ring being substituted with 0-2 R 6 ; R 12 is selected from H, Ci-Cε alkyl, C 1 -C 4 alkoxycarbonyl, Ci-Cβ alkylcarbonyl, Ci-Cβ alkylsulfonyl, aryl (C 1 -C 4 alkyl) sulfonyl, arylsulfonyl, aryl, pyridylcarbonyl or pyridylmethylcarbonyl, wherein said aryls are optionally substituted with 0-3 substituents selected from the group consisting of: C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halo, CF3, and NO2; and R 13 is H. [10] Specifically preferred compounds of this second embodiment are compounds, or pharmaceutically acceptable salt or prodrug forms thereof, selected from: 3 (R, S) - { 5 (R,S)-N- [3- (4-amidinophenyl) isoxazolin-5- ylacetyl]amino}-3-phenylpropanoic acid; 3 (R, S)-{5 (R f S)-N- [3- (4-amidinophenyl) isoxazolin-5- ylacetyl]amino}-pentanoic acid; 3 (R)-{5 (R, S) -N- [3- (4-amidinophenyl) isoxazolin-5- ylacetyl]aminoJheptanoic acid; 3 (i?,S)-{5 (R, S) -N- [3- (4-amidinophenyl) isoxazolin-5- ylacetyl]amino}-4- (phenylthio)butanoic acid; 3 (R, S)-{5 (R, S) -N- [3- (4-amidinophenyl) isoxazolin-5- ylacetyl]amino}-4- (phenylsulfonamido)butanoic acid; 3 (R, S)-{5 (R, S) -N- [3- (4-amidinophenyl) isoxazolin-5- ylacetyl]amino}-4- (n-butylsulfonamido)butanoic acid; 3 (S)-{5 (R, S)-N- [3-(4-amidinophenyl) isoxazolin-5- ylacetyl]amino}-3- (adamantylmethylaminocarbonyl)propanoic acid; 3 (S)-{5 (R,S)-N- [3- (4-amidinophenyl) isoxazolin-5- ylacetyl]amino}-3- (1- azabicyclo[3.2.2]nonylcarbonyl)propanoic acid; 3 (S)-{5 (J?,5)-N- [3- (4-amidinophenyl) isoxazolin-5- ylacetyl]amino}-3- (phenethylaminocarbonyl)propanoic acid. 3 (i?)-{5 (R,S)-N-[3- (4-amidinophenyl) isoxazolin-5- ylacetyl]amino}-3- (3-pyridylethyl)propanoic acid. 3 (Λ)-{5 (R f S)-N- [3- (4-amidinophenyl) isoxazolin-5- ylacetyl]amino}-3- (2-pyridylethyl)propanoic acid. 3 (i?)-{5 (i.,S)-N- [3- (4-amidinophenyl) isoxazolin-5- ylacetyl]amino}-3- (phenylpropy1)propanoic acid. [11] Also preferred compounds of the second embodiment are those compounds of Formula Ic: (Ic) wherein: b is a single or double bond; R 1 is selected from R 2a (R 3 )N-, R 2 (R 3 )N(R 2 N=) C-, R 2a ( 3) N (CH 2 ) q Z-, R 2 (R 3 )N(R 2 N=)C(CH 2 ) q Z-, R 2 (R )N(R 2 N=)CN(R 2 )-, or Z is selected from a bond (i.e. is absent), 0, or S; R 2 and R 3 are independently selected from H, aryl(Cι~Cιo alkoxy) carbonyl, or Ci-Cio alkoxycarbonyl; R 2a is 2 or R 2( R 3) N ( R 2 N =) C; U is a single bond (i.e., ϋ is not present), V is selected from: a single bond (i.e., V is not present); -(C1-C7 alkyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; -(C2-C7 alkenyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; -(C2-C7 alkynyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; - (phenyl)-Q-, said phenyl substituted with 0-2 groups independently selected from R 6 or R 7 ; - (pyridyl)-Q-, said pyridyl substituted with 0-2 groups independently selected from R 6 or R 7 ; or - (pyridazinyl) -Q-, said pyridazinyl substituted with 0-2 groups independently selected from R 6 or R 7 ' Q is selected from a single bond (i.e., Q is not present), -0-, -S(0) m -, -N(R 12 )-, -(CH 2 ) m -, -C(=0)-, -N(R 5a )C(=0)-, -C(=0)N(R 5a )-, -CH2O-, -OCH2-, -CH 2 N (R 12 ) -, -N (R 12 ) CH 2 - , -CH 2 C (=0) - , -C (=0) CH 2 -, -CH 2 S (0) m - , or -S (0) m CH 2 - , provided that when b is a single bond, and R 1 -U-V- is a substituent on C5 of the central 5-membered ring in Formula I, then Q is not -0-, -S(0) m -, -N(R 12 )-, -C(=0)N(R 5a )-, -CH2O-, CH2N(R 12 )- or -CH 2 S(0) m -; W is selected from: -(C(R 4 ) 2 )-C(=0)-N(R 5a )-, or -C(=0)-N(R 5a )-(C(R 4 ) 2 )-; X is -C(R 4 )2~CHR 4a -; R 4 is selected from H, C 1 -C 1 0 alkyl, C 1 -C 1 0 alkylcarbonyl, aryl, arylalkyl, cycloalkyl, or cycloalkylalkyl; R a is selected from hydroxy, C 1 -C 1 0 alkoxy, nitro, -N(R 5 )R 5a , -N(R 12 )R 13 , or -N(R 16 )R 17 , C 1 -C 1 0 alkyl substituted with 0-3 R 6 , aryl substituted with 0-3 R 6 , heteroaryl substituted with 0-3 R 6 , or C1-C 1 0 alkylcarbonyl; R 4b is selected from H, Ci-Cβ alkyl, C2-C6 alkenyl, C2- Cβ alkynyl, hydroxy, Ci-Cβ alkoxy, Ci-Cβ alkylthio, Ci-Cβ alkylsulfinyl, Ci-Cδ alkylsulfonyl, nitro, C 1 -C6 alkylcarbonyl, Cβ-Cio aryl, -N(R 12 )R 13 , halo, CF3 f CN, Ci-Cβ alkoxycarbonyl, carboxy, piperidinyl, morpholinyl or pyridyl; R 5 is selected from H or C 1 -C 1 0 alkyl substituted with 0-6 R b ; R 5a is selected from hydrogen, hydroxy, Ci to Cβ alkyl, C 2 to C6 alkenyl, C3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl, Ci-Cβ alkoxy, benzyloxy, Cβ to Cio aryl, heteroaryl, heteroarylalkyl, C 7 to Cn arylalkyl, or adamantylmethyl, C 1 -C 1 0 alkyl substituted with 0-2 R b ; alternately, R 5 and R 5a can be taken together to be 3- azabicyclononyl, 1,2,3, 4-tetrahydro-l-quinolinyl, 1,2,3, 4-tetrahydro-2-isoquinolinyl, 1-piperidinyl, 1-morpholinyl, 1-pyrrolidinyl, thiamorpholinyl, thiazolidinyl or 1-piperazinyl, each being optionally substituted with C 1 -C6 alkyl, Cβ-Cio aryl, heteroaryl, C 7 -C 11 arylalkyl, Ci-Cβ alkylcarbonyl, C3-C 7 cycloalkylcarbonyl, Ci-Cε alkoxycarbonyl or C 7 -C 11 arylalkoxycarbonyl; R 5b is selected from Ci-Cβ alkyl, C 2 -C6 alkenyl, C3-C 11 cycloalkyl, C 4 -C 11 cycloalkylmethyl, Cβ-Cio aryl, 7 -C 11 arylalkyl, or C 1 -C 10 alkyl substituted with 0-2 R b Y is selected from hydroxy, Ci to Cio alkyloxy, C3 to Cn cycloalkyloxy, C6 to Cio aryloxy, C 7 to Cn aralkyloxy, C3 to Cio alkylcarbonyloxyalkyloxy, C3 to Cio alkoxycarbonyloxyalkyloxy, C2 to Cio alkoxycarbonylalkyloxy, C5 to Cio cycloalkylcarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonyloxyalkyloxy, C5 to CIQ cycloalkoxycarbonylalkyloxy, C 7 to Cn aryloxycarbonylalkyloxy, Cβ to C 12 aryloxycarbonyloxyalkyloxy, Cβ to C 1 2 arylcarbonyloxyalkyloxy, C5 to Cio alkoxyalkylcarbonyloxyalkyloxy, C 5 to Cio (5-alkyl- l,3-dioxa-cyclopenten-2-one-yl)methyloxy, or Cio to C 14 (5-aryl-l,3-dioxa-cyclopenten-2-one- yl)methyloxy; R 6 and R 7 are each independently selected from H, Ci-Cio alkyl, hydroxy, Ci-Cio alkoxy, nitro, Ci-Cio alkylcarbonyl, -N(R 1 )R 13 , cyano, or halo; R 12 and R 13 are each independently selected from H, i-Cio alkyl, Cι~Cιo alkoxycarbonyl, Ci-Cio alkylcarbonyl, Cι~Cιo alkylsulfonyl, aryl (Ci-Cio alkyl) sulfonyl, arylsulfonyl, heteroarylcarbonyl, heteroarylalkylcarbonyl or aryl, wherein said aryls are optionally substituted with 0-3 substituents selected from the group consisting of: C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halo, CF3, and NO2; R 15 is selected from H, C 1 -C 1 0 alkyl, C 2 -C 1 0 alkenyl, C 2 -C 1 0 alkynyl, C 1 -C 1 0 alkoxy, aryl, heteroaryl or C 1 -C 1 0 alkoxycarbonyl, CO2R 5 or -C (=0)N (R 5 )R 5a ; R 16 is selected from: -C(=0)-0-R 18a , -C(=0)-R 18b , -C(=0)N(R 18b ) 2 , -S02-R 18a , or -S0 2 -N(R 18b ) 2 ; R 17 is selected from: H or C 1 -C 4 alkyl; R i8a s selected from: Ci-Cβ alkyl substituted with 0-2 R 19 , C 2 -C8 alkenyl substituted with 0-2 R 19 , C2-C8 alkynyl substituted with 0-2 R 19 , C3-C8 cycloalkyl substituted with 0-2 R 19 , aryl substituted with 0-4 R 19 , aryl (Ci-C δ alkyl)- substituted with 0-4 R 19 , a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, triazolyl, imidazolyl, benzofuranyl, indolyl, indolinyl, quinolinyl, isoquinolinyl, isoxazolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyrimidinyl, 3H-indolyl, carbazolyl, pyrrolidinyl, piperidinyl, indolinyl, or morpholinyl, said heterocyclic ring being substituted with 0-4 R 19 ; Cι~C6 alkyl substituted with a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolinyl, benzofuranyl, indolyl, indolenyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyridinyl, 3H-indolyl, indolyl, carbazole, pyrrolidinyl, piperidinyl, indolinyl, or morpholinyl, said heterocyclic ring being substituted with 0-4 R 19 ; l 8 b is selected from R 18a or H; R 19 is selected from H, halogen, CF 3 , CN, NO2, NR 12 R 13 , Ci-Cβ alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Ci-Cβ alkoxy, C3-C 11 cycloalkyl, C 4 -C 11 cycloalkylalkyl, aryl, heteroaryl, aryl (Ci-Cβ alkyl)-, or C 1 -C 4 alkoxycarbonyl; n is 0-4; q is 1-7; r is 0-3; provided that n, q, and r are chosen such that the number of atoms between R 1 and Y is in the range of 8-17. [12] Further preferred compounds of the second embodiment of Formula Ic are those compounds of Formula lb: (lb) wherein : R 1 is selected from: R 2 <R 3 )N-, R 2 NH(R 2 N=) C-, R 2 NH(R 2 N=)CNH-, R 2 R 3 N (CH2) p > Z-, R 2 NH(R 2 N=)CNH(CH 2 )p«Z- or V is a single bond (i.e., V is not present), -(phenyl)- or -(pyridyl)-; W is selected from: -(C(R 4 ) 2 )-C(=0)-N(R 5a )-, -C(=0)-N(R 5a )-CH 2 -; X is selected from: -CH2-CHN(R 16 )R 17 -, or -CH 2 -CHNR 5 R 5a -; Y is selected from: hydroxy; Ci to Cio alkoxy; methylcarbonyloxymethoxy-; ethylcarbonyloxymethoxy-; t-butylcarbonyloxymethoxy-; cyclohexylcarbonyloxymethoxy-; 1- (methylcarbonyloxy)ethoxy-; 1-(ethylcarbonyloxy)ethoxy-; 1- (t-butylcarbonyloxy) ethoxy-; 1- (cyclohexylcarbonyloxy)ethoxy-; i-propyloxycarbonyloxymethoxy-; t-butyloxycarbonyloxymethoxy-; 1- (i-propyloxycarbonyloxy)ethoxy-; 1- (cyclohexyloxycarbonyloxy)ethoxy-; 1- (t-butyloxycarbonyloxy)ethoxy-; dimethylaminoethoxy-; diethylaminoethoxy-; (5-methyl-l, 3-dioxacyclopenten-2-on-4-yl)methoxy-; (5- (t-butyl) -1,3-dioxacyclopenten-2-on-4- yl)methoxy-; ( 1 , 3-dioxa-5-phenyl-cyclopent en-2-on-4-y 1 ) methoxy- ; 1- (2- (2-methoxypropyl) carbonyloxy) ethoxy- ; R 16 is selected from: -C (=0) -0-R 18a , -C (=0) -R 18b , -S (=0) 2 -R 18a or -S02~N (R 18b ) 2 ; R 17 is selected from H or C 1 -C 5 alkyl; R l8a is selected from: Ci-Cβ alkyl substituted with 0-2 R 19 , C 2 -C8 alkenyl substituted with 0-2 R 19 , C 2 -C8 alkynyl substituted with 0-2 R 19 , C3-C 8 cycloalkyl substituted with 0-2 R 19 , aryl substituted with 0-4 R 19 , aryl(Cι-C6 alkyl)- substituted with 0-4 R 19 , a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, triazolyl, imidazolyl, benzofuranyl, indolyl, indolinyl, quinolinyl, isoquinolinyl, isoxazolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyrimidinyl, 3H-indolyl, carbazolyl, pyrrolidinyl, piperidinyl, indolinyl, or morpholinyl, said heterocyclic ring being substituted with 0-4 R 19 ; Ci-Cβ alkyl substituted with a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolinyl, benzofuranyl, indolyl, indolenyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyridinyl, 3#-indolyl, indolyl, carbazole, pyrrolidinyl, piperidinyl, indolinyl, or morpholinyl, said heterocyclic ring being substituted with 0-4 R 19 . [13] Further preferred compounds of Formula lb are those compounds wherein: R 1 is R 2 NH(R 2 N=)C- or R 2 HN(R 2 N=) CNH- and V is phenylene or pyridylene; or and V is a single bond (i.e. V is absent) ; n is 1 or 2; R l8a i s selected from: C 1 -C 4 alkyl substituted with 0-2 R 19 , C 2 -C 4 alkenyl substituted with 0-2 R 19 , C 2 -C 4 alkynyl substituted with 0-2 R 19 , C3-C 7 cycloalkyl substituted with 0-2 R 19 , aryl substituted with 0-4 R 19 , aryl(Cι-C 4 alkyl)- substituted with 0-4 R 19 , a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, triazolyl, imidazolyl, benzofuranyl, indolyl, indolinyl, quinolinyl, isoquinolinyl, isoxazolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyrimidinyl, 3H-indolyl, carbazolyl, pyrrolidinyl, piperidinyl, indolinyl, isoxazolinyl or morpholinyl, said heterocyclic ring being substituted with 0-4 R 19 ; C 1 -C 4 alkyl substituted with a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolinyl, benzofuranyl, indolyl, indolenyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyridinyl, 3H-indolyl, indolyl, carbazole, pyrrolidinyl, piperidinyl, indolinyl, isoxazolinyl or morpholinyl, said heterocyclic ring being substituted with 0-4 R 19 . [14] Specifically preferred compounds of Formula lb are compounds, or pharmaceutically acceptable salt forms thereof, selected from: N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }- acetyl]-N2- (phenylsulfonyl)-2, 3- (S) - diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } - acetyl]-N2- (4-methyl-phenyl-sulfonyl)-2,3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } - acetyl]-N2- (butanesulfonyl)-2,3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S)-yl}- acetyl]-N2- (propanesulfonyl) -2,3- (S)- diaminopropanoic acid; N 3 -[2-{3-(4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }- acetyl]-N2- (ethanesulfonyl)-2,3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } ~ acetyl]-N2- (methyloxycarbony1)-2, 3- (S) - diaminopropanoic acid; N 3 - [2-{3-(4-formamidinophenyl)-isoxazolin-5 (R, S)-yl}- acetyl]-N2- (ethyloxycarbonyl) -2, 3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } ~ acetyl]-N2- (1-propyloxycarbonyl)-2,3- (S) - diaminopropanoic acid; N 3 -[2-{3-(4-formamidinophenyl)-isoxazolin-5 (R, S)-yl}- acetyl]-N2- (2-propyloxycarbonyl)-2,3- (S) - diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } ~ acetyl]-N2- (n-butyloxycarbonyl)-2, 3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R) -yl }- acetyl]-N2- (n-butyloxycarbonyl)-2, 3- (S)- diaminopropanoic acid; N 3 -[2-{3-(4-formamidinophenyl) -isoxazolin-5 (S^-yl}- acetyl]-N2- (n-butyloxycarbonyl) -2, 3- (S) - diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R) -yl }- acetyl]-N2- (n-butyloxycarbonyl)-2, 3- (R)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (S^-yl}- acetyl]-N2-(n-butyloxycarbonyl)-2, 3-(R)- diaminopropanoic acid; N 3 -[2-{3-(4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }~ acetyl]-N2- (2-butyloxycarbonyl)-2, 3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }~ acetyl]-N2- (1- (2-methyl)-propyloxycarbonyl)-2,3- (S)-diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } - acetyl]-N2- (2-(2-methyl)-propyloxycarbonyl)-2,3- (S)-diaminopropanoic acid; N 3 -[2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } - acetyl]-N2- (benzyloxycarbonyl) -2, 3- (S)- diaminopropanoic acid; N 3 - [2-{3-(4-formamidinophenyl)-isoxazolin-5 (R) -yl }- acetyl]-N2- (benzyloxycarbony1)-2,3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl) -isoxazolin-5 (S) -yl } - acetyl]-N2- (benzyloxycarbonyl)-2, 3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } ~ acetyl]-N2- (4-methylbenzyloxycarbonyl)-2, 3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S)-yl}- acetyl]-N2- (4-methoxybenzyloxycarbonyl)-2, 3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl) -isoxazolin-5 (R, S)-yl}- acetyl]-N2- (4-chlorobenzyloxycarbonyl)-2, 3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }- acetyl]-N2- (4-bromobenzyloxycarbonyl)-2,3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S)-yl}- acetyl]-N2- (4-fluorobenzyloxycarbonyl)-2,3- (S)- diaminopropanoic acid; N 3 - [2-{3-(4-formamidinophenyl)-isoxazolin-5 (R, S)-yl}- acetyl]-N2- (4-phenoxybenzyloxycarbonyl)-2, 3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }~ acety1]-N2- (2- (methyloxyethyl)-oxycarbonyl)-2,3- (S)-diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } - acetyl]-N2- (2-pyridinylcarbonyl)-2, 3- (S) - diaminopropanoic acid; N 3 - [2-{3-(4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }~ acetyl]-N2-(3-pyridinylcarbonyl)-2,3-(S)- diaminopropanoic acid; N 3 — [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } ~ acetyl]-N2- (4-pyridinyl-carbonyl)-2,3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } - acetyl]-N2- (2- (2-pyridinyl)-acetyl)-2,3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } ~ acetyl]-N2- (2- (3-pyridinyl)-acetyl)-2,3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } - acetyl]-N2- (2- (4-pyridinyl)-acetyl)-2, 3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }- acetyl]-N2- (2-pyridyl-methyloxycarbonyl)-2,3- (S) - diaminopropanoic acid; N 3 - [2-{3-(4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }- acetyl]-N2- (3-pyridyl-methyloxycarbony1)-2, 3- (S) - diaminopropanoic acid; N 3 — [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S)-yl}- acetyl]-N2- (4-pyridyl-methyloxycarbonyl)-2,3- (S)- diaminopropanoic acid. N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }- acetyl]-N2- (4-butyloxyphenylsulfonyl)-2, 3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } ~ acetyl]-N2- (2-thienylsulfonyl)-2,3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S)-yl}- acetyl]-N2- (3-methylphenylsulfonyl)-2,3- (R,S)- diaminopropanoic acid; N 3 -[2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S)-yl}- acetyl]-N2-(3-methylphenylsulfonyl)-2,3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }- acetyl]-N2- (3-methylphenylsulfonyl)-2,3- (R)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R) -yl }- acetyl]-N2- (3-methylphenylsulfonyl)-2, 3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (S) -yl ) - acetyl]-N2- (3-methylphenylsulfonyl)-2, 3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (S) -yl } - acetyl]-N2- (3-methylphenylsulfonyl)-2,3- (R)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl) -isoxazolin-5 (R) -yl } - acetyl]-N2- (3-methylphenylsulfonyl) -2,3- (R)- diaminopropanoic acid; N 3 - [2-{3-(4-formamidinophenyl)-isoxazolin-5 (R, S)-yl}- acetyl]-N2-(4-iodophenylsulfonyl)-2,3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S)-yl}- acetyl]-N2- (3-trifluoromethylphenylsulfonyl)-2,3- (S)-diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } - acetyl]-N2- (3-chlorophenylsulfonyl)-2, 3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } ~ acetyl]-N2- (3-2-methoxycarbonylphenylsulfonyl) -2, 3- (S)-diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } - acetyl]-N2- (2,4, 6-trimethylphenylsulfonyl) -2, 3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }~ acetyl]-N2- (2-chlorophenylsulfonyl)-2, 3- (S) - diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S)-yl}- acetyl]-N2- (4-trifluoromethylphenylsulfonyl)-2,3- (S)-diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } - acetyl]-N2- (2-trifluoromethylphenylsulfonyl)-2,3- (S)-diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S)-yl}- acetyl]-N2- (2-fluorophenylsulfonyl)-2, 3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } - acetyl]-N2- (4-fluorophenylsulfonyl)-2,3-(S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinoρhenyl)-isoxazolin-5 (R, S)-yl}- acetyl]-N2- (4-methoxyphenylsulfonyl) -2,3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinoρhenyl)-isoxazolin-5 (R, S) -yl }~ acetyl]-N2- (2,3,5, 6-tetramethylphenylsulfonyl)-2,3- (S)-diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } - acetyl]-N2- (4-cyanophenylsulfonyl)-2,3- (S)- diaminopropanoic acid; N 3 -[2-{3-(4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }- acetyl]-N2- (4-chlorophenylsulfonyl)-2, 3- (S)- diaminopropanoic acid; N 3 -[2-{3-(4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }~ acetyl]-N2- (4-propylphenylsulfonyl)-2, 3- (S)- diaminopropanoic acid; N 3 -[2-{3-(4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }- acetyl]-N2- (2-ρhenylethylsulfonyl)-2,3- (S) - diaminopropanoic acid; N 3 - [2-{3-(4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }- acetyl]-N2- (4-isopropylphenylsulfonyl)-2, 3- (S)- diaminopropanoic acid; N 3 -[2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S)-yl}- acetyl]-N2- (3-phenylpropylsulfonyl)-2,3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }- acetyl]-N2- (3-pyridylsulfonyl)-2,3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }- acetyl]-N2- (phenylaminosulfonyl)-2,3- (S)- diaminopropanoic acid; N 3 - [2-{3-(4-formamidinophenyl)-isoxazolin-5 (R, S) -yl )- acetyl]-N2- (benzylaminosulfonyl) -2, 3- (S) - diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl )- acetyl]-N2- (dimethylaminosulfonyl)-2,3- (S) - diaminopropanoic acid, N 3 - [2-{3-(2-fluoro-4-formamidinophenyl)-isoxazolin- 5(Λ,S -yl}-acetyl]-N2-(3-methylphenylsulfonyl)-2,3- (S)-diaminopropanoic acid, N 3 -[2-{3- (2-formamidino-5-pyridinyl)-isoxazolin-5 (R, S) - yl}-acetyl]-N2- (n-butyloxycarbonyl)-2,3- (S)- diaminopropanoic acid, N 3 -[2-{3- (2-formamidino-5-pyridinyl) -isoxazolin-5 (R, S) - yl}-acetyl]-N2- (3-methylphenylsulfonyl)-2, 3- (S)- diaminopropanoic acid, N 3 - [2-{3- (3-formamidino-6-pyridinyl) -isoxazolin-5 (R, S) - y1}-acetyl]-N2-(n-butyloxycarbonyl)-2,3-(S)- diaminopropanoic acid, N 3 -[2-{3- (3-formamidino-6-pyridinyl)-isoxazolin-5 (R, S) - yl}-acetyl]-N2- (3-methylphenylsulfonyl) -2,3- (S)- diaminopropanoic acid, N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S)-yl}- acetyl]-N2- (phenylaminocarbonyl)-2, 3- (S) - diaminopropanoic acid; N 3 - [2-(3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl } ~ acetyl]-N2- (4-fluorophenylaminocarbonyl) -2, 3- (S) - diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }- acetyl]-N2- (1-naphthylaminocarbonyl) -2,3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }- acetyl]-N2- (benzylaminocarbonyl)-2,3- (S) - diaminopropanoic acid; N 3 -[2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }- acetyl]-N2- (3-bromo-2-thienylsulfonyl)-2, 3- (S)- diaminopropanoic acid; N 3 - [2-{3- (4-formamidinoρhenyl)-isoxazolin-5 (R, S) -yl } ~ acetyl]-N2- (3-methyl-2-benzothienylsulfonyl)-2,3- (S)-diaminopropanoic acid, N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S) -yl }- acetyl]-N2- (isobutyloxycarbonyl)-2,3- (S)- diaminopropanoic acid, N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R) -yl }- acetyl]-N2- (isobutyloxycarbonyl) -2, 3- (S)- diaminopropanoic acid, N 3 - [2-{3- (4-formamidinoρhenyl)-isoxazolin-5 (S) -yl }- acetyl]-N2- (isobutyloxycarbonyl)-2, 3- (S) - diaminopropanoic acid, N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R, S)-yl}- acetyl]-N2- (2-cyclopropylethoxycarbonyl)-2,3- (S) - diaminopropanoic acid, N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (R)-yl}- acetyl]-N2- (2-cyclopropylethoxycarbonyl)-2,3- (S) - diaminopropanoic acid, and N 3 - [2-{3- (4-formamidinophenyl)-isoxazolin-5 (S) -yl }- acetyl]-N2- (2-cyclopropylethoxycarbonyl)-2,3- (S) - diaminopropanoic acid. N 3 - [2-{3- (4-guanidinophenyl) -isoxazolin-5 (R, S)-yl}- acetyl]-N2- (n-butyloxycarbonyl)-2, 3- (S)- diaminopropanoic acid. N 3 - [2-{3- (4-guanidinophenyl)-isoxazolin-5 (R) -yl }- acetyl]-N2- (n-butyloxycarbonyl)-2, 3- (S)- diaminopropanoic acid. N 3 - [2-{3- (4-guanidinophenyl)-isoxazolin-5 (R) -yl }- acetyl]-N2-(3-methylphenylsulfonyl)-2,3- (S)- diaminopropanoic acid. N 3 - [2-{5- (4-formamidinophenyl)-isoxazolin-3 (R, S) -yl } - acetyl]-N2- (n-butyloxycarbonyl)-2, 3- (S)- diaminopropanoic acid; [15] Also specifically preferred are prodrug esters of the specifically preferred compounds of Formula lb, said esters being chosen from the group consisting of: methyl; ethyl; isopropyl; methylcarbonyloxymethyl-; eth lcarbonyloxymethyl-; t-butylcarbonyloxymethy1-; cyclohexylcarbonyloxymethyl-; 1- (methylcarbonyloxy)ethyl-; 1- (ethylcarbonyloxy)ethyl-; 1- (t-butylcarbonyloxy) ethyl-; 1-(cyclohexylcarbonyloxy)ethyl-; i-propyloxycarbonyloxymethyl-; cyclohexylcarbonyloxymethyl-; t-butyloxycarbonyloxymethyl-; 1- (i-propyloxycarbonyloxy)ethyl-; 1- (cyclohexyloxycarbonyloxy) ethyl-; 1- (t-butyloxycarbonyloxy)ethyl-; dimethylaminoethy1-; diethylaminoethyl-; ( 5-methyl-l , 3-dioxacyclopenten-2-on-4-yl) methyl- ; ( 5- (t-butyl ) -1 , 3-dioxacyclopenten-2-on- 4-yl ) methyl- ; ( 1 , 3-dioxa-5-phenyl-cyclopenten-2-on-4-yl) methyl- ; 1- (2- ( 2-methoxypropyl ) carbonyloxy) ethyl- . [ 16] A third embodiment of this invention provides a compound of Formula Id : or a pharmaceutically acceptable salt or prodrug form thereof wherein: R 1 is selected from is selected from R 2 (R 3 )N-, R 2 (R 3 )N(R 2 N=)C-, R 2 (R 3 )N(R 2 N=)CN(R 2 )-, R 2 (R 3 )N(CH 2 ) q Z-, R 2 (R 3 )N(R 2 N=) C(CH 2 ) q Z-, R 2 (R 3 )N(R 2 N=)CN(R 2 ) (CH 2 ) q Z-, piperazinyl- (CH 2 ) q Z-, or Z is selected from a bond (i.e., is absent), 0, S, S(=0), or S(=0) 2 ; R 2 and R 3 are independently selected from: H, C 1 -C 10 alkyl, C 2 -Cg alkenyl, C3-C 11 cycloalkyl, C 4 -C 11 cycloalkylalkyl, C 6 -Cι 0 aryl, C 7 -C 11 aryla lk y l , C 2 -C 7 alkylcarbonyl, C 7 -C 11 arylcarbonyl, C 2 -C 1 0 alkoxycarbonyl, C 4 -C 11 cycloalkoxycarbonyl, C 7 -C 11 bicycloalkoxycarbonyl, C 7 -C 11 aryloxycarbonyl, or aryl (Ci-Cio alkoxy) carbonyl, Ci-Cε alkylcarbonyloxy(C 1 -C 4 alkoxy) carbonyl, Cβ-Cio arylcarbonyloxy(C 1 -C 4 alkoxy) carbonyl, C 4 -C 1 1 cycloalkylcarbonyloxy(C 1 -C 4 alkoxy) carbonyl; U is selected from: a single bond (i.e., U is absent) C 1 -C 7 alkylene, C 2 -C 7 alkenylene, C 2 -C 7 alkynylene, arylene substituted with 0-3 R 6a , , or pyridylene substituted with 0-3 R 6a ; V is selected from: a single bond (i.e., V is absent); C 1 -C 7 alkylene substituted with 0-6 R 6 or R 7 ; C 2 -C 7 alkenylene substituted with 0-4 R 6 or R 7 ; C2-C 7 alkynylene substituted with 0-4 R 6 or R 7 ; phenylene substituted with 0-4 R 6 or R 7 ; pyridylene substituted with 0-3 R 6 or R 7 ; pyridazinylene substituted with 0-3 R 6 or R 7 ; X is selected from: a single bond (i.e., X is absent); -(CH 2 ) n C(=0)N(R 12 )-; C1-C 7 alkylene substituted with 0-6 R 4 , R 8 or R 15 ; C2-C 7 alkenylene substituted with 0-4 R 4 , R 8 or R 15 ; C2-C 7 alkynylene substituted with 0-4 R 4 , R 8 or R 15 ; Y is selected from: hydroxy, Ci to Cio alkyloxy, C3 to Cn cycloalkyloxy, Cβ to Cio aryloxy, C 7 to Cn aralkyloxy, C3 to Cio alkylcarbonyloxyalkyloxy, C3 to Cio alkoxycarbonyloxyalkyloxy, C 2 to Cio alkoxycarbonylalkyloxy, C 5 to Cio cycloalkylcarbonyloxyalkyloxy, C5 to Cio cycloalkoxycarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonylalkyloxy, C 7 to Cn aryloxycarbonylalkyloxy, Cβ to C 12 aryloxycarbonyloxyalkyloxy, Cβ to C 12 arylcarbonyloxyalkyloxy, C 5 to Cio alkoxyalkylcarbonyloxyalkyloxy, C 5 to Cio (5-alkyl-l,3-dioxa-cyclopenten-2-one- yl)methyloxy, Cio to C 14 (5-aryl-l,3-dioxa-cyclopenten-2-one- y1)methyloxy; (R 2 ) (R 3 )N-(Cι-Cιo alkoxy)-; R 14 and W are attached to the same carbon and taken together to form a spiro-fused, 5-7 membered ring structure of the formula: D, E, F and G are each independently selected from: C(R6 a ) 2 ; carbonyl; a heteroatom moiety selected from N, N(R 12 ), O, provided that no more than 2 of D, E, F and G are N, N(R 12 ), 0, S, or C (=0) ; alternatively, the bond between D and E, E and F, or F and G in such spiro-fused ring may be a carbon-nitrogen double bond or a carbon-carbon double bond; R 4 is selected from H, Ci-Cio alkyl, hydroxy, Ci-Cio alkoxy, nitro, Ci-Cio alkylcarbonyl, or -N(R 12 )R 13 ; R 6 and R 7 are each independently selected from H, C -Cio alkyl, hydroxy, Cι~Cιo alkoxy, nitro, Cι~Cιo alkylcarbonyl, -N(R 12 )R 13 , cyano, halo, CF3, CHO, Cθ2R 5a , C(=0)R 5a , CONHR 5a , CON(R 12 )2, OC(=0)R 5a , OC(=0)OR 5a , 0R 5a , OC(=0)N(R 12 ) 2 , 0CH 2 C02R 5a , C02CH 2 C02R 5a , N(R 12 ) 2 , NO2, NR 12 C (=0)R 5a , NR 12 C(=0)OR 5a , NR 12 C(=0)N(R 12 )2, NR 12 S02N (R 12 ) , NR 12 Sθ2R 5a , S(0) p R 5a , Sθ2N(R 12 ) 2 , C2 to Cβ alkenyl, C3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl; Cβ to Cio aryl optionally substituted with 1-3 groups selected from halogen, Ci-Cβ alkoxy, Ci-Cβ alkyl, CF3, S(0)mMe, or -NMe2; C 7 to Cn arylalkyl, said aryl being optionally substituted with 1-3 groups selected from halogen, C1-C6 alkoxy, C1-C6 alkyl, CF 3 , S(0) m Me, or -NMβ2; methylenedioxy when R 6 is a substituent on aryl; R 6a is selected from C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halo, CF3, NO 2 , or NR 12 R 13 ; R 8 is selected from: H; R 6 ; C 1 -C 1 0 alkyl, substituted with 0-8 R 6 ; C 2 -C 1 0 alkenyl, substituted with 0-6 R 6 ; C 2 -C 1 0 alkynyl, substituted with 0-6 R 6 ; C3-C8 cycloalkyl, substituted with 0-6 R 6 ; C5-C6 cycloalkenyl, substituted with 0-5 R 6 ; aryl, substituted with 0-5 R 6 ; 5-6 membered heterocyclic ring containing 1-2 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, artially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-5 R 6 ; R 12 and R 13 are independently H, Cι~Cιo alkyl, Cι~Cιo alkoxycarbonyl, Cι~Cιo alkylcarbonyl, Cι~Cιo alkylsulfonyl, aryl (Cι~Cιo alkyl) sulfonyl, arylsulfonyl, aryl, C 2 -C6 alkenyl, C3-C 11 cycloalkyl, C4-C11 cycloalkylalkyl, C7-C 1 1 arylalkyl, C 2 -C 7 alkylcarbonyl, C 7 -C 11 arylcarbonyl, C2-C 1 0 alkoxycarbonyl, C 4 -C 11 cycloalkoxycarbonyl, C 7 -C 11 bicycloalkoxycarbonyl, C 7 -C 11 aryloxycarbony1, heteroarylcarbonyl, heteroarylalkylcarbonyl or aryl (C 1 -C 10 alkoxy) carbonyl, wherein said aryls or heteroaryls are optionally substituted with 0-3 substituents selected from the group consisting of: C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halo, CF3, and NO 2 ; R 5 and R 5a are selected independently from H, Ci to Cβ alkyl, C 2 to Cβ alkenyl, C3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl, Cβ to Cio aryl, C 7 to Cn arylalkyl, or C 1 -C 1 0 alkyl substituted with 0-8 R 4 ; R 15 is selected from: H; R 6 ; C 1 -C 1 0 alkyl, substituted with 0-8 R 6 ; C 2 -C 10 alkenyl, substituted with 0-6 R 6 ; 1 -C 1 0 alkoxy, substituted with 0-6 R 6 ; aryl, substituted with 0-5 R 6 ; 5-6 membered heterocyclic ring containing 1-2 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-5 R 6 ; Ci-Cio alkoxycarbonyl substituted with 0-8 R 6 ; CO2R 5 ; or -C(=0)N(R 12 )R 13 ; provided that n, p, q and r are chosen such that the number of atoms between R 1 and Y is in the range of 8-17. [17] Preferred compounds of this third embodiment are compounds of Formula III: wherein: R 1 is selected from R 2 HN-, H2N(R 2 N=)C-, H2N(R 2 N=) CNH-, R 2 H (CH 2 ) q O~, H2N(R 2 N=)CNH(CH 2 ) q O-, piperazinyl-(CH2)qO-, R 2 is selected from H, aryl (C 1 -C 10 alkoxy) carbonyl, or 1 -C 1 0 alkoxycarbonyl; R 4 is selected from H, Ci-Cio alkyl, hydroxy, Ci-Cio alkoxy, nitro, Ci-Cio alkylcarbonyl, or -N(R 12 )R 13 ; V is selected from: a single bond (i.e., V is absent); C 1 -C 7 alkylene substituted with 0-6 R 6 or R 7 ; C2-C 7 alkenylene substituted with 0-4 R 6 or R 7 ; C 2 -C 7 alkynylene substituted with 0-4 R 6 or R 7 ; phenylene substituted with 0-3 R 6 or R 7 ; pyridylene substituted with 0-3 R 6 or R 7 ; pyridazinylene substituted with 0-3 R 6 or R 7 ; X is selected from - (CH 2 ) n C (=0)N(R 12 )-, C 1 -C 7 alkylene substituted with 0-1 R 4 , C 2 -C 7 alkenylene, or C 2 -C 7 alkynylene; Y is selected from: hydroxy, Ci to Cio alkyloxy, C3 to Cn cycloalkyloxy, C6 to Cio aryloxy, C 7 to Cn aralkyloxy, C3 to Cio alkylcarbonyloxyalkyloxy, C 3 to Cio alkoxycarbonyloxyalkyloxy, C2 to Cio alkoxycarbonylalkyloxy, C5 to Cio cycloalkylcarbonyloxyalkyloxy, C5 to Cio cycloalkoxycarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonylalkyloxy, C 7 to Cn aryloxycarbonylalkyloxy, Cβ to C 12 aryloxycarbonyloxyalkyloxy, Cβ to C 12 arylcarbonyloxyalkyloxy, C 5 to Cio alkoxyalkylcarbonyloxyalkyloxy, C 5 to Cio (5-alkyl-l,3-dioxa-cyclopenten-2-one- yl)methyloxy, or Cio to C 14 (5-aryl-l, 3-dioxa-cyclopenten-2-one- yl)methyloxy; Z is selected from 0 or CH 2 ; D, E, F and G are each independently selected from: CH 2 ; carbonyl; a heteroatom moiety selected from N, NH, 0, provided that no more than 2 of D, E, F and G are N, NH, O or S; alternatively, the bond between D and E, E and F, or F and G in such spiro-fused ring may be a carbon-nitrogen double bond or a carbon-carbon double bond; R 6 and R 7 are each independently selected from H, C1-C10 alkyl, hydroxy, C 1 -C 1 0 alkoxy, nitro, C 1 -C 1 0 alkylcarbonyl, -N(R 12 )R 13 , cyano, or halo; R 12 and R 13 are each independently selected from H, C1-C10 alkyl, C 1 -C 1 0 alkoxycarbonyl, C1-C10 alkylcarbonyl, C 1 -C 1 0 alkylsulfonyl, aryl (C1-C10 alkyl) sulfonyl, arylsulfonyl, heteroarylcarbonyl, heteroaryalkylcarbonyl or aryl; provided that n, p, q and r are chosen such that the number of atoms between R 1 and Y is in the range of 8-17. [18] Further preferred compounds of this third embodiment are compounds of Formula II wherein: is R 2 NHC(=NR 2 )- and V is phenyl or pyridyl or and V is a single bond (i.e. V is absent) ; n is 1 or 2; X is C 1 -C 4 alkylene substituted with 0-1 R 4 ; Y is selected from: hydroxy; Ci to Cio alkoxy; methylcarbonyloxymethoxy-; ethylcarbonyloxymethoxy-; t-butylcarbonyloxymethoxy-; cyclohexylcarbonyloxymethoxy-; 1- (methylcarbonyloxy)ethoxy-; 1- (ethylcarbonyloxy)ethoxy-; 1- (t-butylcarbonyloxy) ethoxy-; 1- (cyclohexylcarbonyloxy)ethoxy-; i-propyloxycarbonyloxymethoxy-; t-butyloxycarbonyloxymethoxy-; 1- (i-propyloxycarbonyloxy)ethoxy-; 1- (cyclohexyloxycarbonyloxy) ethoxy-; 1- ( -butyloxycarbonyloxy) ethoxy-; dimethylaminoethoxy-; diethylaminoethoxy-; (5-methyl-l,3-dioxacyclopenten-2-on-4-yl)methoxy-; (5- (t-butyl)-1,3-dioxacyclopenten-2-on-4- yl)methoxy-; (1, 3-dioxa-5-phenyl-cyclopenten-2-on-4-yl)methoxy-; 1- (2- (2-methoxypropyl) carbonyloxy) ethoxy-; R 12 and R 13 are each independently selected from H, Ci-Cβ alkyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkylsulfonyl, aryl (C 1 -C 4 alkyl) sulfonyl, arylsulfonyl, heteroarylcarbonyl, heteroaryalkylcarbonyl or aryl; and R 13 is H. [19] Specifically preferred compounds of this third embodiment are compounds, or pharmaceutically acceptable salt or prodrug forms thereof, selected from: 5 (JR,S)-3-(4-amidinophenyl)-8- (2-carboxyethyl)-l-oxa-2, 8- diazaspiro [ .4]non-2-ene-7, 9-dione; 5 (R, S)-3-(4-amidinophenyl)-8- (3-carboxypropyl)-1-oxa- 2, 8-diazaspiro[4.4]non-2-ene-7, 9-dione; 5 (i?,S)-3-(4-amidinophenyl)-8- (2-carboxyethyl)-l-oxa-2, 8- diazaspiro[4.4]non-2-ene-5-one; 5 (R, S)-3- (4-amidinophenyl)-8- (3-carboxypropyl)-1-oxa- 2,8-diazaspiro[4.4]non-2-ene-5-one; 5 (R, S)-3- (4-amidinophenyl)-8- (2-carboxyethyl)-l-oxa-2- azaspiro[4.4]nona-2, 8-diene-5-one; 5 (R, S) -3-(4-amidinophenyl)-8- (3-carboxypropyl)-l-oxa-2- azaspiro[4.4]nona-2, 8-diene-5-one; 5 (R, S)-3-(4-amidinophenyl)-8- (2-carboxyethyl)-l-oxa-2, 8- diazaspiro [4.4]dec-2-ene-7, 9-dione; 5 (R, S) -3-(4-amidinophenyl)-8- (3-carboxypropyl)-1-oxa- 2, 8-diazaspiro[4.4]dec-2-ene-7, 9-dione; 5 (R, S)-3- (4-amidinophenyl)-8- (2-carboxyethyl)-l-oxa-2, 8- diazaspiro[4.4]dec-2-ene-5-one; 5 (R, S)-3- (4-amidinophenyl)-8- (3-carboxyproρyl)-1-oxa- 2, 8-diazaspiro[4.4]dec-2-ene-5-one; 5 (R, S) -3- (4-amidinophenyl)-8- (2-carboxyethyl) -l-oxa-2- azaspiro[4.4]deca-2, 8-diene-5-one; 5 (R, S) -3- (4-amidinophenyl)-8- (3-carboxypropyl)-l-oxa-2- azaspiro[4.4]deca-2, 8-diene-5-one; 5 (R, S)-3- (4-amidinophenyl)-8- (2-carboxyethyl)-l-oxa-2, 8- diazaspiro [4.4]undec-2-ene-7, 9-dione; 5 (R, S) -3- (4-amidinophenyl)-8- (3-carboxypropyl)-1-oxa- 2,8-diazaspiro [4.4]undec-2-ene-7, 9-dione; 5 (R,S)-3-(4-amidinophenyl)-8- (2-carboxyethyl)-l-oxa-2, 8- diazaspiro [4.4]undec-2-ene-5-one; 5 (R, S)-3- (4-amidinophenyl)-8- (3-carboxypropyl)-1-oxa- 2, 8-diazaspiro[4.4]undec-2-ene-5-one; 5 (R, S) -3- (4-amidinophenyl)-8- (2-carboxyethyl)-l-oxa-2- azaspiro[4.4]undeca-2, 8-diene-5-one; 5 (R, S)-3- (4-amidinophenyl)-8- (3-carboxypropyl)-l-oxa-2- azaspiro[4.4]undeca-2, 8-diene-5-one; 5 (R, S)-3- [2- (piperidin-4-yl)ethyl]-8- (2-carboxyethyl)-1- oxa-2, 8-diazaspiro[4.4]non-2-ene-7, 9-dione; 5 (R, S) -3- [2- (piperidin-4-yl)ethyl]-8- (3-carboxypropyl) - l-oxa-2, 8-diazaspiro[4.4]non-2-ene-7, 9-dione; 5 (R, S)-3- [2- (piperidin-4-yl) ethyl]-8- (2-carboxyethyl)-1- oxa-2, 8-diazaspiro[4.4]non-2-ene-5-one; 5 (R, S)-3-[2-(piperidin-4-yl)ethyl]-8- (3-carboxypropyl) - l-oxa-2, 8-diazaspiro[4. ]non-2-ene-5-one; 5 (R, S)-3- [2- (piperidin-4-yl)ethyl]-8- (2-carboxyethyl)-1- oxa-2-azaspiro[4.4]nona-2, 8-diene-5-one; 5 (R, S) -3- [2- (piperidin-4-yl)ethyl]-8- (3-carboxypropyl) - l-oxa-2-azaspiro [4.4]nona-2, 8-diene-5-one; 5 (R. S)-3- [2- (piperidin-4-yl)ethyl]-8- (2-carboxyethyl)-1- oxa-2, 8-diazaspiro[4.4]dec-2-ene-7, 9-dione; 5 (R, S) -3- [2- (piperidin-4-yl)ethyl]-8- (3-carboxypropyl) - l-oxa-2,8-diazaspiro[4.4]dec-2-ene-5, 7-dione; 5 (R, S) -3- [2- (piperidin-4-yl)ethyl]-8- (2-carboxyethyl)-1- oxa-2, 8-diazaspiro[4.4]dec-2-ene-5-one; 5 (R, S) -3- [2- (piperidin-4-yl)ethyl]-8- (3-carboxypropyl) - l-oxa-2, 8-diazaspiro[4.4]dec-2-ene-5-one; 5 (R, S)-3- [2- (piperidin-4-yl)ethyl]-8- (2-carboxyethyl)-1- oxa-2-azaspiro[4.4]deca-2, 8-diene-5-one; 5 (R, S) -3- [2- (piperidin-4-yl)ethyl]-8- (3-carboxypropyl) - l-oxa-2-azaspiro [4.4]deca-2, 8-diene-5-one; 5 (R, S)-3-[2- (piperidin-4-yl)ethyl]-8- (2-carboxyethyl)-1- oxa-2, 8-diazaspiro[4.4]undec-2-ene-7, 9-dione; 5 (R. S) -3- [2- (piperidin-4-yl)ethyl]-8- (3-carboxypropyl) - l-oxa-2, 8-diazaspiro[4.4]undec-2-ene-7, 9-dione; 5 (J ,S)-3- [2- (piperidin-4-yl)ethyl]-8- (2-carboxyethyl)-1- oxa-2, 8-diazaspiro[4.4]undec-2-ene-5-one; 5 (R, S) -3- [2- (piperidin-4-yl)ethyl]-8- (3-carboxypropyl) - l-oxa-2, 8-diazaspiro[4.4]undec-2-ene-5-one; 5 (R, S)-3- [2- (piperidin-4-yl)ethyl]-8- (2-carboxyethyl)-1- oxa-2-azaspiro[ .4]undeca-2, 8-diene-5-one; 5 (R, S)-3- [2- (piperidin-4-yl)ethyl]-8- (3-carboxypropyl) - l-oxa-2-azaspiro[4.4]undeca-2, 8-diene-5-one; 5 (R,S)-3- (4-amidinophenyl)-8- [2- (benzyloxycarbonylamino)-2-carboxyethyl]-1-oxa- 2,8-diazaspiro[4.5]dec-2-ene. [20] A fourth embodiment of this invention provides compounds of Formula I: or pharmaceutically acceptable salt or prodrug forms thereof, wherein: R 1 is selected from: R (R 3 )N(CH 2 ) q Z-, R 2 (R 3 )N(R 2 N=)C(CH 2 ) q Z-, R 2 (R 3 )N(R 2 N=)CN(R 2 ) (CH 2 ) q Z-, piperazinyl- (CH 2 ) q Z- or Z is selected from O, S, S (=0) , S(=0)2; R 2 and R 3 are independently selected from: H, Cι~Cιo alkyl, C 2 -C6 alkenyl, C3-C 11 cycloalkyl, C4-C11 cycloalkylalkyl, C6-C 1 0 aryl, C7-C11 arylalkyl, C2-C7 alkylcarbonyl, C 7 -C 11 arylcarbonyl, C2-C 1 0 alkoxycarbonyl, C 4 -C 11 cycloalkoxycarbonyl, C 7 -C 11 bicycloalkoxycarbonyl, C 7 -C 11 aryloxycarbony1, or aryl (C 1 -C 1 0 alkoxy) carbonyl, C 1 -C6 alkylcarbonyloxy(C 1 -C 4 alkoxy) carbonyl, Cβ-Cio arylcarbonyloxy(C 1 -C 4 alkoxy) carbonyl, C 4 -C 11 cycloalkylcarbonyloxy(C 1 -C 4 alkoxy) carbonyl; U is optionally present and is selected from C 1 -C 7 alkylene, C2-C 7 alkenylene, C 2 -C 7 alkynylene, arylene, or pyridylene; V is selected from: a single bond (i.e., V is absent); C 1 -C 7 alkylene substituted with 0-6 R 6 or R 7 ; C2-C 7 alkenylene substituted with 0-4 R 6 or R 7 ; C2-C 7 alkynylene substituted with 0-4 R 6 or R 7 ; phenylene substituted with 0-4 R 6 or R 7 ; pyridylene substituted with 0-3 R 6 or R 7 ; pyridazinylene substituted with 0-3 R 6 or R 7 ; W is -(aryl)-Z 1 -, wherein said aryl is substituted with 0-6 R 6 or R 7 ; Z 1 is selected from a single bond (i.e., Z 1 is absent), -CH2-, O or S; X is selected from: a single bond (i.e., X is absent); C 1 -C 7 alkylene substituted with 0-6 R 4 , R 8 or R 15 ; C 2 -C 7 alkenylene substituted with 0-4 R 4 , R 8 or R 15 ; C 2 -C 7 alkynylene substituted with 0-4 R 4 , R 8 or R 15 ; Y is selected from hydroxy, Ci to Cio alkyloxy, C3 to Cn cycloalkyloxy, Cβ to Cio aryloxy, C 7 to Cn aralkyloxy, C3 to Cio alkylcarbonyloxyalkyloxy, C3 to Cio alkoxycarbonyloxyalkyloxy, C 2 to Cio alkoxycarbonylalkyloxy, C 5 to Cio cycloalkylcarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonylalkyloxy, C 7 to Cn aryloxycarbonylalkyloxy, Cβ to C 1 2 aryloxycarbonyloxyalkyloxy, Cβ to C 12 arylcarbonyloxyalkyloxy, C 5 to C o alkoxyalkylcarbonyloxyalkyloxy, C5 to Cio (5-alkyl- 1, 3-dioxa-cyclopenten-2-one-yl)methyloxy, Cio to C 14 (5-aryl-l,3-dioxa-cyclopenten-2-one-yl)methyloxy; (R 2 ) (R 3 )N-(Cι-Cιo alkoxy)-; R 4 is selected from H, C 1 -C 1 0 alkyl, hydroxy, C 1 -C 1 0 alkoxy, nitro, C 1 -C 1 0 alkylcarbonyl, or -N(R 12 )R 13 ; R 6 and R 7 are each independently selected from H, C 1 -C 10 alkyl, hydroxy, C 1 -C 1 0 alkoxy, nitro, C -C 1 0 alkylcarbonyl, -N(R 12 )R 13 , cyano, halo, CF3, CHO, Cθ2R 5a , C(=0)R 5a , CONHR 5a , CON(R 12 ) 2 , OC(=0)R 5a , OC(=0)OR 5a , OR 5a , OC(=0)N(R 12 ) 2 , 0CH C0 2 R 5a , Cθ2CH 2 C0 2 R 5a , N(R 12 ) 2 , N0 2 , NR 12 C (=0)R 5a , NR 12 C(=0)0R 5a , NR 12 C(=0)N(R 12 ) 2 , NR 12 S0 2 N(R 12 ) 2 , NR 12 Sθ2R 5a , S(0) p R 5a , Sθ2N(R 12 ) 2 , C 2 to C 6 alkenyl, C3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl; Cβ to Cio aryl optionally substituted with halogen, alkoxy, alkyl, -CF3, S(0)mMe, or -NMe 2 ; or C 7 to Cn arylalkyl said aryl being optionally substituted with halogen, alkoxy, alkyl, -CF 3 , S(0)mMe, or - Me 2 ; R 8 is selected from: H; R 6 ; C 1 -C 1 0 alkyl, substituted with 0-8 R 6 ; C2-C 1 0 alkenyl, substituted with 0-6 R 6 ; C2~ ιo alkynyl, substituted with 0-6 R 6 ; C3-C8 cycloalkyl, substituted with 0-6 R 6 ; C 5 -C6 cycloalkenyl, substituted with 0-5 R 6 ; aryl, substituted with 0-5 R 6 ; 5-6 membered heterocyclic ring containing 1-2 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-5 R 6 ; R 12 and R 13 are independently H, C 1 -C 10 alkyl, C 1 -C 10 alkoxycarbonyl, C 1 -C 10 alkylcarbonyl, C 1 -C 1 0 alkylsulfonyl, aryl (C 1 -C 1 0 alkyl) sulfonyl, arylsulfonyl, aryl, C 2 -C 6 alkenyl, C3-C 11 cycloalkyl, C 4 -C 11 cycloalkylalkyl, C 7 -C 11 ary l a lk y l , C2 _ C 7 alkylcarbonyl, C 7 -C 11 arylcarbonyl, C 2 -C 1 0 alkoxycarbonyl, C 4 -C 11 cycloalkoxycarbonyl, C 7 -C 11 bicycloalkoxycarbonyl, C 7 -C 11 aryloxycarbonyl, heteroarylcarbonyl, heteroarylalkylcarbonyl or aryl (C 1 -C 1 0 alkoxy) carbonyl; R 14 is selected from H, Ci-Cio alkyl, C 2 -C 1 0 alkenyl, C 2 -C 1 0 alkynyl, C -C 1 0 alkoxy, aryl, heteroaryl or C-ι-C- 1 0 alkoxycarbonyl, C0 R 5 or -C (=0)N(R 12 )R 13 ; R 5 and R 5a are selected independently from H, Ci to Cβ alkyl, C 2 to Cβ alkenyl, C3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl, C6 to Cio aryl, C 7 to Cn arylalkyl, or C 1 -C 1 0 alkyl substituted with 0-8 R 4 ; R 15 is selected from: H; R6; C 1 -C 10 alkyl, substituted with 0-8 R 6 ; C 2 -C 10 alkenyl, substituted with 0-6 R 6 ; C 1 -C 10 alkoxy, substituted with 0-6 R 6 ; aryl, substituted with 0-5 R 6 ; 5-6 membered heterocyclic ring containing 1-2 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-5 R 6 ; C 1 -C 1 0 alkoxycarbonyl substituted with 0-8 R 6 ; CO2R 5 ; or -C(=0)N(R 12 )R 13 ; provided that n, q, and r are chosen such that the number of atoms between R 1 and Y is about 8-17. [21] Preferred compounds of this fourth embodiment are those of Formula IV: wherein : R 1 is selected from R 2 HN (CH 2 ) q O- , R 2 HN (R 2 N=C) NH (CH 2 ) q O- , piperazinyl- (CH 2 ) q O- , or Z is O; R 2 is selected from H, aryl (Ci-Cio) alkoxycarbonyl, Ci-Cio alkoxycarbonyl; V is selected from: a single bond (i.e., V is absent); C 1 -C 7 alkylene substituted with 0-6 R 6 or R 7 ; C 2 -C 7 alkenylene substituted with 0-4 R 6 or R 7 ; C2-C 7 alkynylene substituted with 0-4 R 6 or R 7 ; phenylene substituted with 0-3 R 6 or R 7 ; pyridylene substituted with 0-3 R 6 or R 7 ; pyridazinylene substituted with 0-3 R 6 or R 7 ; Z 1 is selected from a single bond (i.e., Z 1 is absent), 0 or S; X is selected from: a single bond (i.e., X is absent); C 1 -C 7 alkylene substituted with 0-4 R 4 , R 8 or R 15 ; C2-C 7 alkenylene substituted with 0-3 R 4 , R 8 or R 15 ; C2-C 7 alkynylene substituted with 0-3 R 4 , R 8 or R 15 ; Y selected from hydroxy, Ci to Cio alkyloxy, C 3 to Cn cycloalkyloxy, Cβ to Cio aryloxy, C 7 to Cn aralkyloxy, C3 to Cio alkylcarbonyloxyalkyloxy, C3 to Cio alkoxycarbonyloxyalkyloxy, C 2 to Cio alkoxycarbonylalkyloxy, C5 to Cio cycloalkylcarbonyloxyalkyloxy, C5 to Cio cycloalkoxycarbonyloxyalkyloxy, C5 to Cio cycloalkoxycarbonylalkyloxy, C 7 to Cn aryloxycarbonylalkyloxy, Cβ to C 1 2 aryloxycarbonyloxyalkyloxy, Cβ to C 12 arylcarbonyloxyalkyloxy, C5 to Cio alkoxyalkylcarbonyloxyalkyloxy, C5 to Cio (5-alkyl- 1,3-dioxa-cyclopenten-2-one-yl)methyloxy, or Cio to C 14 (5-aryl-l,3-dioxa-cyclopenten-2-one- yl)methyloxy; R 4 is selected from H, C 1 -C 1 0 alkyl, hydroxy, C1-C10 alkoxy, nitro, C 1 -C 1 0 alkylcarbonyl, or -N(R 12 )R 13 ; R 6 and R 7 are selected from H, C 1 -C 1 0 alkyl, hydroxy, 1 -C 1 0 alkoxy, nitro, C 1 -C 1 0 alkylcarbonyl, -N(R 12 )R 13 , cyano, or halo; R 8 is selected from H, C 1 -C 1 0 alkyl, C 2 -C 10 alkenyl, C3-C8 cycloalkyl, C 5 -C6 cycloalkenyl, aryl, 5-6 membered heterocyclic ring containing 1-2 N, 0, or S, where said heterocyclic ring may be saturated, partially saturated, or fully unsaturated; R 12 and R 13 are independently selected from H, C 1 -C 1 0 alkyl, C 1 -C 1 0 alkoxycarbonyl, C 1 -C 1 0 alkylcarbonyl, C 1 -C 1 0 alkylsulfonyl, aryl(Cι~Cιo alkyl) sulfonyl, arylsulfonyl, heteroarylcarbonyl, heteroarylalkylcarbonyl or aryl; R 14 is selected from H, Ci-Cio alkyl, C2-C 1 0 alkenyl, C 2 -C 1 0 alkynyl, C 1 -C 1 0 alkoxy, aryl, heteroaryl or C 1 -C 1 0 alkoxycarbonyl, CO2R 5 or -C (=0)N(R 12 )R 13 ; R 5 is selected from H or C 1 -C 1 0 alkyl substituted with 0-6 R 4 ; n is 0-4; q is 2-7; provided that n and q are chosen such that the number of atoms between R 1 and Y is in the range of 8-17. [22] Further preferred compounds of this fourth embodiment are compounds of Formula IV wherein: R 1 is R 2 HN(CH ) q O- or V is C 1 -C3 alkylene; Z 1 is a single bond (i.e. Z 1 is absent) or 0; X is C 1 -C3 alkylene substituted with 0-1 R 4 ; Y is selected from: hydroxy; Ci to Cio alkoxy; methylcarbonyloxymethoxy-; ethylcarbonyloxymethoxy-; t-butylcarbonyloxymethoxy-; cyclohexylcarbonyloxymethoxy-; 1- (methylcarbonyloxy) ethoxy-; 1-(ethylcarbonyloxy)ethoxy-; 1- (t-butylcarbonyloxy) ethoxy-; 1- (cyclohexylcarbonyloxy)ethoxy-; i-propyloxycarbonyloxymethoxy-; t-butyloxycarbonyloxymethoxy-; 1- (i-propyloxycarbonyloxy)ethoxy-; 1- (cyclohexyloxycarbonyloxy) ethoxy-; 1- (t-butyloxycarbonyloxy)ethoxy-; dimethylaminoethoxy-; diethylaminoethoxy-; (5-methyl-l,3-dioxacyclopenten-2-on-4-yl)methoxy-; (5- (t-butyl)-1,3-dioxacyclopenten-2-on-4- yl)methoxy-; (1,3-dioxa-5-phenyl-cyclopenten-2-on-4-yl)methoxy-; 1- (2- (2-methoxypropyl) carbonyloxy) ethoxy-; R 12 and R 13 are independently selected from H, Cι~C6 alkyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyl, C 1 -C6 alkylsulfonyl, aryl (C 1 -C 4 alkyl) sulfonyl, arylsulfonyl, heteroarylcarbonyl, heteroarylalkylcarbonyl or aryl; R 13 is H. [23] Specifically preferred compounds of this fourth embodiment are compounds, or pharmaceutically acceptable salt or prodrug forms thereof, selected from: 5 (JR,S)-4- [3- (piperidin-4-yl) oxymethylisoxazolin-5-yl]hy- drocinnamic acid; 5 (JR,S)-4- [3- (2-aminoethoxymethyl) isoxazolin-5-yl]hydro- cinnamic acid; 5 (R, S) - .- [3- (3-aminopropyloxymethyl) isoxazolin-5-yl]hy- drocinnamic acid; 5 (R, S)-4- [3- (piperidin-4-yl)oxymethylisoxazolin-5- yl]phenoxyacetic acid; 5 (R,S)-.-[3- (2-aminoethoxymethyl) isoxazolin-5-yl]phen- oxyacetic acid; 5 (R, S)-4- [3- (3-aminopropyloxymethyl) isoxazolin-5- yl]phenoxyacetic acid. [24] A fifth embodiment of this invention provides a compound of Formula I : or a pharmaceutically acceptable salt or prodrug form thereof wherein: b is a single or double bond; R 1 is selected from R 2a (R 3 )N-, R 2 (R 3 )N (R 2 N=) C-, R 2a ( R 3) N (CH 2 ) q Z-, R 2 (R 3 )N (R 2 N=) C (CH 2 ) q Z-, Z is selected from a bond (i.e. is absent), 0, S, S(=0), s(=0) 2 ; R 2 and R 3 are independently selected from: H, Cι~Cιo alkyl, C2-C6 alkenyl, C3-C 11 cycloalkyl, C 4 -C 11 cycloalkylalkyl, C 6 -Cι 0 aryl, C7-C 11 ary l a l kyl, C2-C7 alkylcarbonyl, C7-C 11 arylcarbonyl, C2-C 1 0 alkoxycarbonyl, C 4 -C 11 cycloalkoxycarbonyl, C 7 -C 11 bicycloalkoxycarbonyl, C 7 -C 11 aryloxycarbony1, aryl (C 1 -C 1 0 alkoxy) carbonyl, alkylcarbonyloxyalkoxycarbonyl, or alkoxycarbonyloxyalkoxycarbonyl, Ci-Cε alkylcarbonyloxy(C 1 -C 4 alkoxy) carbonyl, Cε-Cio arylcarbonyloxy(C 1 -C 4 alkoxy)carbonyl, C 4 -C 11 cycloalkylcarbonyloxy(C 1 -C 4 alkoxy)carbonyl; R 2a i s R 2 or R 2 (R3) N ( R 2 N= ) C . U is selected from: a single bond (i.e., U is not present), -(C 1 -C 7 alkyl)-, -(C- 2 -C 7 alkenyl)-, -(C2-C7 alkynyl)-, -(aryl)- substituted with 0-3 R 6a , or -(pyridyl)- substituted with 0-3 R 6a ; V is selected from: a single bond (i.e., V is not present); -(C 1 -C 7 alkyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; -(C2-C 7 alkenyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; -(C2-C 7 alkynyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; -(phenyl)-, substituted with 0-2 groups independently selected from R 6 or R 7 ; -(pyridyl)-, substituted with 0-2 groups independently selected from R 6 or R 7 ; or -(pyridazinyl)-, substituted with 0-2 groups independently selected from R 6 or R 7 ; W is selected from : X is selected from: a single bond (i.e. X is absent) -(C(R 4 )2) n -C(R 4 ) (R 8 )-C(R 4 ) (R 4a )-, with the proviso that when n is 0 or 1, then at least one of R a or R 8 is other than H or methyl; Y is selected from: hydroxy, Ci to Cio alkyloxy, C3 to Cn cycloalkyloxy, C6 to Cio aryloxy, C 7 to Cn aralkyloxy, C3 to Cio alkylcarbonyloxyalkyloxy, C3 to Cio alkoxycarbonyloxyalkyloxy, C2 to Cio alkoxycarbonylalkyloxy, C5 to Cio cycloalkylcarbonyloxyalkyloxy, C5 to Cio cycloalkoxycarbonyloxyalkyloxy. C5 to Cio cycloalkoxycarbonylalkyloxy, C 7 to Cn aryloxycarbonylalkyloxy, Cβ to C 12 aryloxycarbonyloxyalkyloxy, Cβ to C 1 2 arylcarbonyloxyalkyloxy, C 5 to Cio alkoxyalkylcarbonyloxyalkyloxy, C 5 to Cio (5-alkyl-l,3-dioxa-cyclopenten-2-one- yl)methyloxy, Cio to C 14 (5-aryl-l,3-dioxa-cyclopenten-2-one- yl)methyloxy, (R 2 ) (R 3 )N-(Cι-Cιo alkoxy)-; Z 1 is -C-, -0-, or -NR 22 -; Z 2 is -0-, or -NR 22 -; R 4 is selected from H, C 1 -C 10 alkyl, C 1 -C 1 0 alkylcarbonyl, aryl, arylalkylene cycloalkyl, or cycloalkylalkylene; alternately, two R 4 groups on adjacent carbons may join to form a bond (i.e. a carbon-carbon double or triple bond) ; R 4a is selected from H, hydroxy, C 1 -C 1 0 alkoxy, nitro, N(R 5 )R 5a , -N(R 12 )R 13 , -N(R 16 )R 17 , C 1 -C 1 0 alkyl substituted with 0-3 R 6 , aryl substituted with 0-3 R 6 , or C 1 -C 1 0 alkylcarbonyl; R 4b is selected from H, Ci-Cε alkyl, C2-C6 alkenyl, C2-C6 alkynyl, hydroxy, Ci-Cβ alkoxy, Ci-Cε alkylthio, Ci-Cδ alkylsulfinyl, Ci-Cβ alkylsulfonyl, nitro, C 1 -C6 alkylcarbonyl, Cβ-Cio aryl, -N(R 12 )R 13 ; halo, CF3, CN, C 1 -C6 alkoxycarbonyl, carboxy, piperidinyl, or pyridyl; R 5 is selected from H, Ci-Cβ alkyl, C2-C6 alkenyl, C3-C 11 cycloalkyl, C4-C 11 cycloalkylmethyl, Cβ-Cio aryl, C 7 -C 11 arylalkyl, or C 1 -C 1 0 alkyl substituted with 0-2 R b ; R 5a is selected from hydrogen, hydroxy, Ci to Cβ alkyl, C2 to Cβ alkenyl, C3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl, Ci-Cβ alkoxy, benzyloxy, Cβ to Cio aryl, heteroaryl, C 7 to Cn arylalkyl, or C 1 -C 1 0 alkyl substituted with 0-2 R b ; alternately, R 5 and R 5a when both are substituents on the same nitrogen atom (as in -NR 5 R 5a ) can be taken together with the nitrogen atom to which they are attached to form 3-azabicyclononyl, 1,2,3,4- tetrahydro-1-quinolinyl, 1,2,3, 4-tetrahydro-2- isoquinolinyl, 1-piperidinyl, 1-morpholinyl, 1- pyrrolidinyl, thiamorpholinyl, thiazolidinyl or 1- piperazinyl, each being optionally substituted with C 1 -C 6 alkyl, Cε-Cio aryl, heteroaryl, C 7 -C 11 arylalkyl, C 1 -C6 alkylcarbonyl, C3-C 7 cycloalkylcarbonyl, Ci-Cβ alkoxycarbonyl, C 7 -C 11 arylalkoxycarbonyl, Ci-Cβ alkylsulfonyl or Cβ-Cio arylsulfonyl; R 5b is selected from C -Cβ alkyl, C2-C6 alkenyl, C3-C 11 cycloalkyl, C 4 -C 11 cycloalkylmethyl, Cε-Cio aryl, C 7 -C 11 arylalkyl, or C 1 -C 1 0 alkyl substituted with 0-2 R 4b ; R 6 is selected from H, C 1 -C 1 0 alkyl, hydroxy, C 1 -C 1 0 alkoxy, nitro, C 1 -C 1 0 alkylcarbonyl, -N(R 12 )R 13 , cyano, halo, CF3, CHO, C0 2 R 5 , C(=0)R 5a , CONR 5 R 5a , OC(=0)R 5a , OC(=0)OR 5b , OR 5 , OC(=0)NR 5 R 5a , OCH 2 C0 2 R 5 , CO2CH2CO2R 5 , N0 , NR 5a C(=0)R 5a , NR 5a C(=0)0R 5b , NR 5a C(=0)NR 5 R 5a , NR 5a S02NR 5 R 5a , NR 5a S0 2 R 5 , S(0) p R 5 , S02NR 5 R 5a , C2 to Cβ alkenyl, C3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl; C6 to Cio aryl optionally substituted with 1-3 groups selected from halogen, Ci-Cβ alkoxy, Ci-Cβ alkyl, CF3, S(0)mMe, or -NMβ2; C 7 to Cn arylalkyl, said aryl being optionally substituted with 1-3 groups selected from halogen, C 1 -C6 alkoxy, Ci-Cε alkyl, CF3, S(0)mMe, or -NMe2; methylenedioxy when R 6 is a substiuent on aryl; or a 5-6 membered heterocyclic ring containing 1-2 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R 7 ; R 6a is selected from C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halo, CF3, NO2, or NR 12 R 13 ; R 7 is selected from H, C 1 -C 1 0 alkyl, hydroxy, C 1 -C 1 0 alkoxy, nitro, C 1 -C 1 0 alkylcarbonyl, -N(R 12 )R 13 , cyano, halo, CF3, CHO, CO2R 5 , C(=0)R 5a , CONR 5 R 5a , 0C(=0)R 5a , 0C(=0)0R 5b , 0R 5a , OC(=0)NR 5 R 5a , OCH2CO2R 5 , CO2CH2CO2R 5 , NO2, NR 5a C(=0)R 5a , NR 5a C(=0)OR 5b , NR 5a C(=0)NR 5 R 5a , NR 5a Sθ2NR 5 R 5a , NR 5a S02R 5 , S(0) m R 5a / S02NR 5 R 5a , C2 to Cε alkenyl, C3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl, Cβ to Cio aryl, or C 7 to Cn arylalkyl; R 8 is selected from: R 6 ; C 2 -C 1 0 alkyl, substituted with 0-3 R 6 ; C2-C 1 0 alkenyl, substituted with 0-3 R 6 ; C2-C 1 0 alkynyl, substituted with 0-3 R 6 ; C3-C8 cycloalkyl, substituted with 0-3 R 6 ; C5-C6 cycloalkenyl, substituted with 0-3 R 6 ; aryl, substituted with 0-3 R 6 ; 5-6 membered heterocyclic ring containing 1-2 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R 6 ; R 12 and R 13 are independently H, C 1 -C 1 0 alkyl, C 1 -C 1 0 alkoxycarbonyl, C 1 -C 1 0 alkylcarbonyl, C 1 -C 1 0 alkylsulfonyl, aryl (C 1 -C 10 alkyl) sulfonyl, arylsulfonyl, aryl, C2-C6 alkenyl, C 3 -C 11 cycloalkyl, C 4 -C 11 cycloalkylalkyl, C7-C11 arylalkyl, C 7 -C 11 arylcarbonyl, C 4 -C1 1 cycloalkoxycarbonyl, C7- C 11 bicycloalkoxycarbonyl, C 7 -C 11 aryloxycarbonyl, or aryl (C 1 -C 1 0 alkoxy)carbonyl, wherein said aryls are optionally substituted with 0-3 substituents selected from the group consisting of: C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halo, CF3, and NO2; R 14 is selected from H, C1-C 1 0 alkyl, C2-C 1 0 alkenyl, C 2 -C 1 0 alkynyl, C 1 -C 1 0 alkoxy, aryl, heteroaryl or C 1 -C 1 0 alkoxycarbonyl, CO2R 5 or -C (=0)N(R 5 )R 5a ; R 15 is selected from: H; R 6 ; C 1 -C 1 0 alkyl, substituted with 0-3 R 6 ; 2 ~ ιo alkenyl, substituted with 0-3 R 6 ; C 1 -C 1 0 alkoxy, substituted with 0-3 R 6 ; aryl, substituted with 0-3 R 6 ; 5-6 membered heterocyclic ring containing 1-2 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R 6 ; i-Cio alkoxycarbonyl substituted with 0-2 R 6 ; -CO2R 5 ; or -C(=0)N(R 12 )R 13 ; provided that when b is a double bond, only one of R 14 or R 15_ is present; R 16 is selected from: -C(=0)-0-R 18a , -C(=0)-R 18b , -C(=0)N(R 18b ) 2 , -C(=0)NHS02R 18a , -C(=0)NHC(=0)R 18b , -C(=0)NHC(=0)0R 18a , -C(=0)NHS02NHR 18b , -C(=S)-NH-R 18b , -NH-C(=0)-0-R 18a , -NH-C(=0)-R 18b , -NH-C(=0)-NH-R 18b , -Sθ2-0-R 18a , -S0 2 -R 18a , -S0 2 -N(18 b )2, -Sθ2-NHC(=0)018 b , -P(=S) (OR 18a ) 2 , -P(=0) (OR 18a ) , -P(=S) (R 18a )2, -P(=0) (R 18a )2, or R 17 is selected from: H, Ci-Cio alkyl, C2-C6 alkenyl, C3- Cn cycloalkyl, C 4 -C 15 cycloalkylalkyl, aryl, aryl(Cι-Cιo alkyl)-; R 18a is selected from: Ci-Cβ alkyl substituted with 0-2 R 19 , C2-C8 alkenyl substituted with 0-2 R 19 , C2-C8 alkynyl substituted with 0-2 R 19 , C3-C8 cycloalkyl substituted with 0-2 R 19 , aryl substituted with 0-4 R 19 , aryl(Cι-C6 alkyl)- substituted with 0-4 R 19 , a 5-10 membered heterocyclic ring system having 1-3 heteroatoms selected independently from 0, S, and N, said heterocyclic ring being substituted with 0-4 R 19 , C 1 -C6 alkyl substituted with a 5-10 membered heterocyclic ring system having 1-3 heteroatoms selected independently from 0, S, and N, said heterocyclic ring being substituted with 0-4 R 19 ; R l 8b i s selected from R 18a or H; R 19 is selected from H, halogen, CF3, CN, NO 2 , NR 12 R 13 , Ci-Cβ alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C11 cycloalkyl, C 4 -C 11 cycloalkylalkyl, aryl, aryl (C 1 -C6 alkyl)-, C 1 -C6 alkoxy, or C 1 -C 4 alkoxycarbonyl; R 20 and R 21 are each independently selected from H, C 1 -C 1 0 alkyl, CO2R 5 , C(=0)R 5a , CONR 5 R 5a , NR 5 C(=0)R 5a , NR 12 R 13 , C2-C6 alkenyl, C3-C 11 cycloalkyl, C 4 -C 11 cycloalkylmethyl, Cε-Cio aryl, or C 7 -C 11 arylalkyl; R 22 is selected from Ci-Cio alkyl, C 2 -C 6 alkenyl, C3-C11 cycloalkyl, C 4 -C 15 cycloalkylalkyl, aryl, aryl(Cι- C 10 alkyl)-; C(=0)R 5a , Cθ 2 R 5b , -C(=0)N(R 5 )R 5a , or a bond to X; provided that n, q and r are chosen such that the number of atoms connecting R 1 and Y is in the range of 8-17. [25] Preferred compounds of this embodiment are those compounds of Formula Ic: (ic) wherein: Z is selected from a bond (i.e. is absent), 0, or S; R 2 is selected from H, aryl(Cι~Cιo alkoxy)carbonyl, or C 1 -C 10 alkoxycarbonyl; U is a single bond (i.e., U is not present); X is -CHR 4a -; R 5 is selected from H or C 1 -C 10 alkyl substituted with 0-6 R 4b ; R 6 and R 7 are each independently selected from H, Ci-Cio alkyl, hydroxy, Ci-Cio alkoxy, nitro, Ci-Cio alkylcarbonyl, -N(R 12 )R 13 , cyano, or halo; R 12 and R 13 are each independently selected from H, Ci-Cio alkyl, Ci-Cio alkoxycarbonyl, Ci-Cio alkylcarbonyl, Cι~Cιo alkylsulfonyl, aryl (Ci-Cio alkyl) sulfonyl, arylsulfonyl, or aryl, wherein said aryls are optionally substituted with 0-3 substituents selected from the group consisting of: C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halo, CF3, and NO2; R 15 is selected from H, C 1 -C 1 0 alkyl, C 2 -C 1 0 alkenyl, C2-C 1 0 alkynyl, C 1 -C 1 0 alkoxy, aryl, heteroaryl or Cι-C- 1 0 alkoxycarbonyl, CO 2 R 5 or -C (=0)N (R 5 )R 5a ; R 16 is selected from: -C(=0)-0-R 18a , -C(=0)-R 18b , -S(=0)2~R 18a ; R 17 is selected from: H or C 1 -C 4 alkyl; Ri8a is selected from: Ci-Cβ alkyl substituted with 0-2 R 19 , C2-C8 alkenyl substituted with 0-2 R 19 , C 2 -C8 alkynyl substituted with 0-2 R 19 , C3-C8 cycloalkyl substituted with 0-2 R 19 , aryl substituted with 0-2 R 19 , aryl(Cι-C6 alkyl)- substituted with 0-2 R 19 , a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, triazolyl, imidazolyl, benzofuranyl, indolyl, indolinyl, quinolinyl, isoquinolinyl, isoxazolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyridinyl, 3H-indolyl, carbazolyl, pyrrolidinyl, piperidinyl, indolinyl, or morpholinyl, said heterocyclic ring being substituted with 0-2 R 19 ; Ci-Cβ alkyl substituted with a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolinyl, benzofuranyl, indolyl, indolenyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyridinyl, 3H-indolyl, indolyl, carbazole, pyrrolidinyl, piperidinyl, indolinyl, or morpholinyl, said heterocyclic ring being substituted with 0-2 R 19 . [26] Further preferred compounds of this embodiment are compounds of Formula lb: (Ib) wherein: R 1 is selected from: R 2 <R 3 )N-, R 2 NH(R 2 N=) C-, R 2 R N(CH2)p»Z-, R 2 NH(R 2 N=)CNH(CH 2 )p'Z-, n is 0-1; p' is 2-4; p" is 4-6; Z is selected from a bond (i.e. is absent) or O; R 3 is H or C 1 -C 5 alkyl; V is a single bond (i.e., V is not present), or -(phenyl)-; X is selected from: -CH2-, -CHN(R 16 )R 17 -, or -CHNR 5 R 5a -; Y is selected from: hydroxy; Ci to Cio alkoxy; methylcarbonyloxymethoxy-; ethylcarbonyloxymethoxy-; t-butylcarbonyloxymethoxy-; cyclohexylcarbonyloxymethoxy-; 1- (methylcarbonyloxy)ethoxy-; 1- (ethylcarbonyloxy)ethoxy-; 1- (t-butylcarbonyloxy)ethoxy-; 1- (cyclohexylcarbonyloxy)ethoxy-; i-propyloxycarbonyloxymethoxy-; t-butyloxycarbonyloxymethoxy-; 1- (i-propyloxycarbonyloxy)ethoxy-; 1- (cyclohexyloxycarbonyloxy) ethoxy-; 1-( -butyloxycarbonyloxy)ethoxy-; dimethylaminoethoxy-; diethylaminoethoxy-; (5-methyl-l,3-dioxacyclopenten-2 ^ on-4-yl)methoxy-; (5- (t-butyl)-1,3-dioxacyclopenten-2-on-4- yl)methoxy-; (l,3-dioxa-5-phenyl-cyclopenten-2-on-4-yl)methoxy-; 1- (2- (2-methoxypropyl) carbonyloxy) ethoxy-; Ri β a i s selected from: C 1 -C 4 alkyl substituted with 0-2 R 19 , C2-C 4 alkenyl substituted with 0-2 R 19 , C2-C 4 alkynyl substituted with 0-2 R 19 , C3-C 4 cycloalkyl substituted with 0-2 R 19 , aryl substituted with 0-2 R 19 , aryl(Cι-C 4 alkyl)- substituted with 0-2 R 19 , a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, triazolyl, imidazolyl, benzofuranyl, indolyl, indolinyl, quinolinyl, isoquinolinyl, isoxazolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyridinyl, 3#-indolyl, carbazolyl, pyrrolidinyl, piperidinyl, indolinyl, or morpholinyl, said heterocyclic ring being substituted with 0-2 R 19 ; Ci-Cβ alkyl substituted with a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolinyl, benzofuranyl, indolyl, indolenyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyridinyl, 3H-indolyl, indolyl, carbazole, pyrrolidinyl, piperidinyl, indolinyl, or morpholinyl, said heterocyclic ring being substituted with 0-2 R 19 . [27] Further preferred compounds of this fifth embodiment are compounds of Formula lb wherein: R 1 is R 2 NH(R 2 N=)C- or R NH(R 2 N=)CNH- and V is phenyl or pyridyl; or R l iIS and V is a single bond (i.e is absent) n is 1-2; R 3 is H or C 1 -C 5 alkyl; X is selected from: -CH2-, -CHN(R 16 )R 17 -, or -CHNR 5 R 5a -; W is selected from: m is 1-3; Y is selected from: hydroxy; Ci to Cio alkoxy; methylcarbonyloxymethoxy-; ethylcarbonyloxymethoxy-; t-butylcarbonyloxymethoxy-; cyclohexylcarbonyloxymethoxy-; 1-(methylcarbonyloxy)ethoxy-; l-(ethylcarbonyloxy)ethoxy-; 1- (t-butylcarbonyloxy) ethoxy-; 1-(cyclohexylcarbonyloxy)ethoxy-; i-propyloxycarbonyloxymethoxy-; t-butyloxycarbonyloxymethoxy-; 1- (i-propyloxycarbonyloxy)ethoxy-; 1-(cyclohexyloxycarbonyloxy)ethoxy-; 1- (t-butyloxycarbonyloxy)ethoxy-; dimethylaminoethoxy-; diethylaminoethoxy-; (5-methyl-l,3-dioxacyclopenten-2-on-4-yl)methoxy-; (5-(t-butyl)-l,3-dioxacyclopenten-2-on-4- yl)methoxy-; (1,3-dioxa-5-phenyl-cyclopenten-2-on-4-yl)methoxy-; 1- (2- (2-methoxypropyl) carbonyloxy) ethoxy-; R 19 is H, halogen, C 1 -C 4 alkyl, C3-C 7 cycloalkyl, cyclopropylmethyl, aryl, or benzyl; R 20 and R 21 are both H; R 22 is H, C 1 -C 4 alkyl or benzyl. [28] Specifically preferred compounds of this fifth embodiment are compounds of Formula lb, or pharmaceutically acceptable salt forms thereof, selected from: 2- (R, S) -2-carboxymethyl-l- { 5- (R, S) -N- [3- (4- amidinophenyl)isoxazolin-5-yl acetyl]piperidine; 2- (R,S)-2-carboxymethyl-l-{5- (R,S)-N- [3- (4- amidinophenyl) isoxazolin-5-yl acetyl]azepine; 2- (R,S)-2-carboxymethyl-l-{5- (R,S)-N-[3- (4- amidinophenyl) isoxazolin-5-yl acetyl]pyrrolidine; 3-(R,S)-carboxymethyl-4-{5-(R,S)-N-[3-(4- amidinophenyl)isoxazolin-5-yl acetyl]piperazine-2- one; 6-(R,S)-carboxymethyl-1-{5- (R,S)-N- [3-(4- amidinophenyl) isoxazolin-5-yl acetyl]piperidine-2- one; 5- (R,S)-carboxymethyl-l-{5- (R,S)-N-[3-(4- amidinophenyl) isoxazolin-5-yl acetyl]pyrrolidine-2- one; 7- (R,S)-carboxymethyl-1-{5- (R,S)-N- [3- (4- amidinophenyl) isoxazolin-5-yl acetyl]azetidine-2- one; 2- (R,S)-carboxymethyl-1-{5- (R,S)-N- [3- (4- amidinophenyl) isoxazolin-5-yl acetyl]ρyrazolidine; 3- (R,S)-carboxymethyl-4-{5-(R,S)-N-[3- (4- amidinophenyl) isoxazolin-5-yl acetyl]morpholine. In the present invention it has been discovered that the compounds of Formula I above are useful as inhibitors of cell-matrix and cell-cell adhesion processes. The present invention includes novel compounds of Formula I and methods for using such compounds for the prevention or treatment of diseases resulting from abnormal cell adhesion to the extracellular matrix which comprises administering to a host in need of such treatment a therapeutically effective amount of such compound of Formula I. In the present invention it has also been discovered that the compounds of Formula I above are useful as inhibitors of glycoprotein Ilb/IIIa (GPIIb/IIIa) . The compounds of the present invention inhibit the activation and aggregation of platelets induced by all known endogenous platelet agonists. The present invention also provides pharmaceutical compositions comprising a compound of Formula I and a pharmaceutically acceptable carrier. The compounds of Formula I of the present invention are useful for the treatment (including prevention) of thromboembolic disorders. The term "thromboembolic disorders" as used herein includes conditions involving platelet activation and aggregation, such as arterial or venous cardiovascular or cerebrovascular thromboembolic disorders, including, for example, thrombosis, unstable angina, first or recurrent myocardial infarction, ischemic sudden death, transient ischemic attack, stroke, atherosclerosis, venous thrombosis, deep vein thrombosis, thrombophlebitis, arterial embolism, coronary and cerebral arterial thrombosis, myocardial infarction, cerebral embolism, kidney embolisms, pulmonary embolisms, or such disorders associated with diabetes, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula I described above. The compounds of Formula I of the present invention may be useful for the treatment or prevention of other diseases which involve cell adhesion processes, including, but not limited to, infammation, bone degradation, rheumatoid arthritis, asthma, allergies, adult respiratory distress syndrome, graft versus host disease, organ transplantation rejection, septic shock, psoriasis, eczema, contact dermatitis, osteoporosis, osteoarthritis, atherosclerosis, tumors, metastasis, diabetic retinopathy, inflammatory bowel disease and other autoimmune diseases. The compounds of Formula I of the present invention may also be useful for wound healing. The compounds of the present invention are useful for inhibiting the binding of fibrinogen to blood platelets, inhibiting aggregation of blood platelets, treating thrombus formation or embolus formation, or preventing thrombus or embolus formation in a mammal. The compounds of the invention may be used as a medicament for blocking fibrinogen from acting at its receptor site in a mammal. Compounds of the invention may be administered to patients where prevention of thrombosis by inhibiting binding of fibrinogen to the platelet membrane glycoprotein complex Ilb/IIIa receptor is desired. They are useful in surgery on peripheral arteries (arterial grafts, carotid endarterectomy) and in cardiovascular surgery where manipulation of arteries and organs, and/or the interaction of platelets with artificial surfaces, leads to platelet aggregation and consumption, and where the aggregated platelets may form thrombi and thromboemboli . The compounds of the present invention may be administered to these surgical patients to prevent the formation of thrombi and thromboemboli . Extracorporeal circulation is routinely used during cardiovascular surgery in order to oxygenate blood. Platelets adhere to surfaces of the extracorporeal circuit . Adhesion is dependent on the interaction between GPIIb/IIIa on the platelet membranes and fibrinogen adsorbed to the surface of the extracorporeal circuit. Platelets released from artificial surfaces show impaired homeostatic function. The compounds of the invention may be administered to prevent such ex vivo adhesion. The compounds of the present invention may be used for other ex vivo applications to prevent cellular adhesion in biological samples. Other applications of these compounds include prevention of platelet thrombosis, thromboembolism, and reocclusion during and after thrombolytic therapy and prevention of platelet thrombosis, thromboembolism and reocclusion after angioplasty of coronary and other arteries and after coronary artery bypass procedures. The compounds of the present invention may also be used to prevent myocardial infarction. The compounds of the present invention are useful as thrombolytics for the treatment of thromboembolic disorders. The compounds of the present invention can also be administered in combination with one or more additional therapeutic agents select from: anti-coagulant or coagulation inhibitory agents, such as heparin or warfarin; anti-platelet or platelet inhibitory agents, such as aspirin, piroxicam, or ticlopidine; thrombin inhibitors such as boropeptides, hirudin or argatroban; or thrombolytic or fibrinolytic agents, such as plasminogen activators, anistreplase, urokinase, or streptokinase. The compounds of Formula I of the present invention can be administered in combination with one or more of the foregoing additional therapeutic agents, thereby to reduce the doses of each drug required to achieve the desired therapeutic effect. Thus, the combination treatment of the present invention permits the use of lower doses of each component, with reduced adverse, toxic effects of each component. A lower dosage minimizes the potential of side effects of the compounds, thereby providing an increased margin of safety relative to the margin of safety for each component when used as a single agent. Such combination therapies may be employed to achieve synergistic or additive therapeutic effects for the treatment of thromboembolic disorders. By "therapeutically effective amount" it is meant an amount of a compound of Formula I that when administered alone or in combination with an additional therapeutic agent to a cell or mammal is effective to prevent or ameliorate the thromboembolic disease condition or the progression of the disease. By "administered in combination" or "combination therapy" it is meant that the compound of Formula I and one or more additional therapeutic agents are administered concurrently to the mammal being treated. When administered in combination each component may be administered at the same time or sequentially in any order at different points in time. Thus, each component may be administered separately but sufficiently closely in time so as to provide the desired therapeutic effect. The term anti-coagulant agents (or coagulation inhibitory agents), as used herein, denotes agents that inhibit blood coagulation. Such agents include warfarin (available as Coumadin™) and heparin. The term anti-platelet agents (or platelet inhibitory agents), as used herein, denotes agents that inhibit platelet function such as by inhibiting the aggregation, adhesion or granular secretion of platelets. Such agents include the various known non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin, ibuprofen, naproxen, sulindac, indomethacin, mefenamate, droxicam, diclofenac, sulfinpyrazone, and piroxicam, including pharmaceutically acceptable salts or prodrugs thereof. Of the NSAIDS, aspirin (acetylsalicyclic acid or ASA) , and piroxicam. Piroxicam is commercially available from Pfizer Inc. TM (New York, NY) , as Feldane . Other suitable anti¬ platelet agents include ticlopidine, including pharmaceutically acceptable salts or prodrugs thereof. Ticlopidine is also a preferred compound since it is known to be gentle on the gastro-intestinal tract in use. Still other suitable platelet inhibitory agents include thromboxane-A2-receptor antagonists and thromboxane-A2-synthetase inhibitors, as well as pharmaceutically acceptable salts or prodrugs thereof. The phrase thrombin inhibitors (or anti-thrombin agents) , as used herein, denotes inhibitors of the serine protease thrombin. By inhibiting thrombin, various thrombin-mediated processes, such as thrombin-mediated platelet activation (that is, for example, the aggregation of platelets, and/or the granular secretion of plasminogen activator inhibitor-1 and/or serotonin) and/or fibrin formation are disrupted. Such inhibitors include boroarginine derivatives and boropeptides, hirudin and argatroban, including pharmaceutically acceptable salts and prodrugs thereof. Boroarginine derivatives and boropeptides include N-acetyl and peptide derivatives of boronic acid, such as C-terminal α-aminoboronic acid derivatives of lysine, ornithine, arginine, homoarginine and corresponding isothiouronium analogs thereof. The term hirudin, as used herein, includes suitable derivatives or analogs of hirudin, referred to herein as hirulogs, such as disulfatohirudin. Boropeptide thrombin inhibitors include compounds described in Kettner et al., U.S. Patent No. 5,187,157 and European Patent Application Publication Number 293 881 A2, the disclosures of which are hereby incorporated herein by reference. Other suitable boroarginine derivatives and boropeptide thrombin inhibitors include those disclosed in PCT Application Publication Number 92/07869 and European Patent Application Publication Number 471 651 A2, the disclosures of which are hereby incorporated herein by reference, in their entirety. The phrase thrombolytics (or fibrinolytic) agents (or thrombolytics or fibrinolytics) , as used herein, denotes agents that lyse blood clots (thrombi) . Such agents include tissue plasminogen activator, anistreplase, urokinase or streptokinase, including pharmaceutically acceptable salts or prodrugs thereof. Tissue plasminogen activator (tPA) is commercially available from Genentech Inc., South San Francisco, California. The term anistreplase, as used herein, refers to anisoylated plasminogen streptokinase activator complex, as described, for example, in European Patent Application No. 028,489, the disclosures of which are hereby incorporated herein by reference herein, in their entirety. Anistreplase is commercially available as Eminase™. The term urokinase, as used herein, is intended to denote both dual and single chain urokinase, the latter also being referred to herein as prourokinase. Administration of the compounds of Formula I of the invention in combination with such additional therapeutic agent, may afford an efficacy advantage over the compounds and agents alone, and may do so while permitting the use of lower doses of each. A lower dosage minimizes the potential of side effects, thereby providing an increased margin of safety. GPIIb/IIIa is known to be overexpressed in metastatic tumor cells. The compounds or combination products of the present invention may also be useful for the treatment, including prevention, of metastatic cancer. The compounds of the present invention are also useful as standard or reference compounds, for example as a quality standard or control, in tests or assays involving the binding of fibrinogen to platelet GPIIb/IIIa. Such compounds may be- provided in a commercial kit, for example, for use in pharmaceutical research involving GPIIb/IIIa. The compounds of the present invention may also be used in diagnostic assays involving platelet GPIIb/IIIa. The compounds herein described may have asymmetric centers. Unless otherwise indicated, all chiral, diastereomeric and racemic forms are included in the present invention. Many geometric isomers of olefins, C=N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. It will be appreciated that compounds of the present invention that contain asymmetrically substituted carbon atoms may be isolated in optically active or racemic forms . It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis, from optically active starting materials. All chiral, diastereomeric, racemic forms and all geometric isomeric forms of a structure are intended, unless the specific stereochemistry or isomer form is specifically indicated. When any variable (for example but not limited to, R 2 , R 4 , R 6 , R 7 , R 8 , R 12 ,and R 14 , n, etc.) occurs more than one time in any constituent or in any formula, its definition on each occurrence is independent of its definition at every other occurrence. Thus, for example, if a group is shown to be substituted with 0-2 R 4 , then said group may optionally be substituted with up to two R 4 and R 4 at each occurrence is selected independently from the defined list of possible R 4 . Also, by way of example, for the group -N(R 5a )2, each of the two R 5a substituents on N is independently selected from the defined list of possible R 5a . Similarly, by way of example, for the group -C(R )2-, each of the two R 7 substituents on C is independently selected from the defined list of possible R 7 . When a bond to a substituent is shown to cross the bond connecting two atoms in a ring, then such substituent may be bonded to any atom on the ring. When a bond joining a substituent to another group is not specifically shown or the atom in such other group to which the bond joins is not specifically shown, then such substituent may form a bond with any atom on such other group. When a substituent is listed without indicating the atom via which such substituent is bonded to the rest of the compound of Formula I, then such substituent may be bonded via any atom in such substituent. For example, when the substituent is piperazinyl, piperidinyl, or tetrazolyl, unless specified otherwise, said piperazinyl, piperidinyl, tetrazolyl group may be bonded to the rest of the compound of Formula I via any atom in such piperazinyl, piperidinyl, tetrazolyl group. Combinations of substituents and/or variables are permissible only if such combinations result in stable compounds. By stable compound or stable structure it is meant herein a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent. The term "substituted", as used herein, means that any one or more hydrogen on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's normal valency is not exceeded, and that the substitution results in a stable compound. When a substitent is keto (i.e., =0), then 2 hydrogens on the atom are replaced. As used herein, "alkyl" is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms (for example, "Ci-Cio" denotes alkyl having 1 to 10 carbon atoms) ; "haloalkyl" is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms, substituted with 1 or more halogen (for example -C V F W where ' v = 1 to 3 and w = 1 to (2v+l)); "alkoxy" represents an alkyl group of indicated number of carbon atoms attached through an oxygen bridge; "cycloalkyl" is intended to include saturated ring groups, including mono-,bi- or poly-cyclic ring systems, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and adamantyl; and "biycloalkyl" is intended to include saturated bicyclic ring groups such as [3.3.0]bicyclooctane, [4.3.0]bicyclononane, [4.4.O]bicyclodecane (decalin) , [2.2.2]bicyclooctane, and so forth. "Alkenyl" is intended to include hydrocarbon chains of either a straight or branched configuration and one or more unsaturated carbon-carbon bonds which may occur in any stable point along the chain, such as ethenyl, propenyl and the like; and "alkynyl" is intended to include hydrocarbon chains of either a straight or branched configuration and one or more triple carbon-carbon bonds which may occur in any stable point along the chain, such as ethynyl, propynyl and the like. The terms "alkylene", "alkenylene", "phenylene", and the like, refer to alkyl, alkenyl, and phenyl groups, respectively, which are connected by two bonds to the rest of the structure of Formula I. Such "alkylene", "alkenylene", "phenylene", and the like, may alternatively and equivalently be denoted herein as "- (alkyl)-", "- (alkyenyl)-" and "-(phenyl)-", and the like. "Halo" or "halogen" as used herein refers to fluoro, chloro, bromo and iodo; and "counterion" is used to represent a small, negatively charged species such as chloride, bromide, hydroxide, acetate, sulfate and the like. As used herein, "aryl" or "aromatic residue" is intended to mean phenyl or naphthyl; the term "arylalkyl" represents an aryl group attached through an alkyl bridge. As used herein, "carbocycle" or "carbocyclic residue" is intended to mean any stable 3- to 7- membered monocyclic or bicyclic or 7- to 14-membered bicyclic or tricyclic or an up to 26-membered polycyclic carbon ring, any of which may be saturated, partially unsaturated, or aromatic. Examples of such carbocyles include, but are not limited to, cyclopropyl, cyclopentyl, cyclohexyl, phenyl, biphenyl, naphthyl, indanyl, adamantyl, or tetrahydronaphthyl (tetralin) . As used herein, the term "heterocycle" or "heterocyclic" is intended to mean a stable 5- to 7- membered monocyclic or bicyclic or 7- to 10-membered bicyclic heterocyclic ring which may be saturated, partially unsaturated, or aromatic, and which consists of carbon atoms and from 1 to 4 heteroatoms independently selected from the group consisting of N, 0 and S and wherein the nitrogen and sulfur heteroatoms may optionally be oxidized, and the nitrogen may optionally be quaternized, and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring. The heterocyclic ring may be attached to its pendant group at any heteroatom or carbon atom which results in a stable structure. The heterocyclic rings described herein may be substituted on carbon or on a nitrogen atom if the resulting compound is stable. Examples of such heterocycles include, but are not limited to, pyridyl (pyridinyl) , pyrimidinyl, furanyl (furyl) , thiazolyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, tetrazolyl, benzofuranyl, benzothiophenyl, indolyl, indolenyl, isoxazolinyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, 4-piperidonyl, pyrrolidinyl, 2- pyrrolidonyl, pyrrolinyl, tetrahydrofuranyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl or octahydroisoquinolinyl, azocinyl, triazinyl, 6H-1,2,5-thiadiazinyl, 2fl,6H-l,5,2- dithiazinyl, thianthrenyl, pyranyl, isobenzofuranyl, chromenyl, xanthenyl, phenoxathiinyl, 2H-pyrrolyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolyl, isoxazolyl, oxazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolizinyl, isoindolyl, 3H-indolyl, indolyl, lH-indazolyl, purinyl, 4#-quinolizinyl, isoquinolinyl, quinolinyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, 4afl-carbazole, carbazole, β-carbolinyl, phenanthridinyl, acridinyl, perimidinyl, phenanthrolinyl, phenazinyl, phenarsazinyl, phenothiazinyl, furazanyl, phenoxazinyl, isochromanyl, chromanyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidinyl, piperazinyl, indolinyl, isoindolinyl, quinuclidinyl, morpholinyl or oxazolidinyl. Also included are fused ring and spiro compounds containing, for example, the above heterocycles. At used herein, the term "heteroaryl" refers to aromatic heterocyclic groups. Such heteroaryl groups are preferably 5-6 membered monocylic groups or 8-10 membered fused bicyclic groups. Examples of such heteroaryl groups include, but are not limited to pyridyl (pyridinyl), pyrimidinyl, furanyl (furyl) , thiazolyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, indolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrimidinyl, pyridazinyl, benzofuranyl, benzothienyl, benzimidazolyl, quinolinyl, or isoquinolinyl. As used herein, "pharmaceutically acceptable salts" refer to derivatives of the disclosed compounds wherein the parent compound of Formula I is modified by making acid or base salts of the compound of Formula I. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. "Prodrugs" are considered to be any covalently bonded carriers which release the active parent drug according to Formula I in vivo when such prodrug is administered to a mammalian subject . Prodrugs of the compounds of Formula I are prepared by modifying functional groups present in the compounds in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent compounds. Prodrugs include compounds of Formula I wherein hydroxyl, amino, sulfhydryl, or carboxyl groups are bonded to any group that, when administered to a mammalian subject, cleaves to form a free hydroxyl, amino, sulfhydryl, or carboxyl group respectively. Examples of prodrugs include, but are not limited to, acetate, formate and benzoate derivatives of alcohol and amine functional groups in the compounds of Formula I, and the like. Examples of representative carboxyl and amino prodrugs are included under the definition of R 2 , R 3 , and Y. The pharmaceutically acceptable salts of the compounds of Formula I include the conventional non- toxic salts or the quaternary ammonium salts of the compounds of Formula I formed, for example, from non- toxic inorganic or organic acids. For example, such conventional non-toxic salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, and the like. The pharmaceutically acceptable salts of the present invention can be synthesized from the compounds of Formula I which contain a basic or acidic moiety by conventional chemical methods. Generally, the salts are prepared by reacting the free base or acid with stoichiometric amounts or with an excess of the desired salt-forming inorganic or organic acid or base in a suitable solvent or various combinations of solvents. The pharmaceutically acceptable salts of the acids of Formula I with an appropriate amount of a base, such as an alkali or alkaline earth metal hydroxide e.g. sodium, potassium, lithium, calcium, or magnesium, or an organic base such as an amine, e.g., dibenzylethylenediamine, trimethylamine, piperidine, pyrrolidine, benzylamine and the like, or a quaternary ammonium hydroxide such as tetramethylammoinum hydroxide and the like. As discussed above, pharmaceutically acceptable salts of the compounds of the invention can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid, respectively, in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Scifincgfi r 17th ed.. Mack Publishing Company, Easton, PA, 1985, p. 1418, the disclosure of which is hereby incorporated by reference. The disclosures of all of the references cited herein are hereby incorporated herein by reference in their entirety. Synthesis The compounds of the present invention can be prepared in a number of ways well known to one skilled in the art of organic synthesis. The compounds of the present invention can be synthesized using the methods described below, together with synthetic methods known in the art of synthetic organic chemistry, or variations thereon as appreciated by those skilled in the art. Preferred methods include, but are not limited to, those described below. All references cited herein are hereby incorporated in their entirety herein by reference. The following abbreviations are used herein: ,9-Ala 3-aminopropionic acid Boc tert-butyloxycarbonyl B0C2O di-tert-butyl dicarbonate BSTFA N,O-bis (trimethylsilyl)trifluoromethyl- acetamide Cbz benzyloxycarbonyl DCC 1,3-dicyclohexylcarbodiimide DEAD diethyl azodicarboxylate DEC 1-(3-dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride DIEA diisopropylethylamine DCHA dicyclohexylamine DCM dichloromethane DMAP 4-dimethylaminopyridine DMF N, N-dimethylforma ide EtOAc ethyl acetate EtOH ethyl alcohol HOBt 1-hydroxybenzotriazole IBCF iso-butyl chloroformate LAH lithium aluminum hydride NCS N-chlorosuccinimide NMM N-methylmorpholine PPh 3 triphenylphosphine pyr pyridine TBTU 2- (lH-Benzotriazol-1-yl)-1, 1,3,3- tetramethyluronium tetrafluoroborate TFA trifluoroacetic acid THF tetrahydrofuran A convenient method for the synthesis of the compounds of this invention utilizes a dipolar cycloaddition of nitrile oxides with appropriate dipolarophiles to prepare the isoxazoline rings present in compounds of Formula I (for reviews of 1,3-dipolar cycloaddition chemistry, see 1,3-Dipolar Cycloaddition Chemistry (Padwa, ed.), Wiley, New York, 1984; Kanemasa and Tsuge, Heterocycles 1990, 2&, 719) . Scheme I describes one synthetic sequence to the compounds of the second embodiment of this invention. An appropriately substituted hydroxylamine is treated with NCS in DMF according to the method of Liu, et al. i.i . nrσ. Chem. 1980, A3., 3916) . The resulting hydroximinoyl chloride is then dehydrohalogenated in situ using TEA to give a nitrile oxide, which undergoes a 1,3-dipolar cycloaddition to a suitably substituted alkene to afford the isoxazoline. Alternatively, the oxime may be oxidatively chlorinated, dehydrochlorinated and the resulting nitrile oxide trapped by a suitable alkene under phase transfer conditions according to the method of Lee (Synthesis 1982, 508) . Hydrolysis of the ester using conventional methods known to one skilled in the art of organic synthesis gives the desired acids. Intermediates containing alkali-sensitive functionality, such as nitrile, may be deesterified with excellent chemoselectivity using sodium trimethylsilanolate according to the procedure of Laganis and Ehenard (Tetrahedron Lett. 1984, 2 , 5831) . Coupling of the resulting acids to an appropriately substituted a- or β- amino ester using standard coupling reagents, such as DCC/HOBt, affords a nitrile-amide. The nitrile is then converted to the amidine via the imidate or thioimidate under standard conditions followed by ester saponification (LiOH, THF/H 2 O) . 3) UOH, THF(aq) An example of a related method of preparation for compounds within the second embodiment of the present invention is illustrated in Scheme la. Conversion of 3- (4-Cyanophenyl)-isoxazolin-5-ylacetic acid to the corresponding amidine, followed by protection as the Boc-derivative and saponification provides 3-(4-Boc- amidinophenyl)isoxazolin-5-ylacetic acid which is coupled with β-amino acid esters as shown. Deprotection provides the desired isoxazolinylacetyl-β-aminoalaninyl esters. Saponification as described above gives the free acids. Sche e la e A further example of the synthesis of compounds within the second embodiment is shown in Scheme lb. Cycloaddition of commerically available 4-cyanostyrene and t-butylformyloxime using the method described by Gree et al. (Bioorganic and Med. Chem. Lett., 1994, 253) provides t-butyl [5-(4-cyanophenyl) isoxazolin-3- yl]acetate. Using the procedures described above, this intermediate is converted to compounds of formula I wherein the isoxazoline ring is in the reverse orientation with respect to the compounds prepared via Schemes I and la. 3. TFA Additional isoxazolinyl acetates useful as starting materials for the preparation of compounds of Formula I, wherein V is - (phenyl)-Q- and Q is other than a single bond, can be prepared by cycloaddition of a suitably substituted chloro or bromooxime with an ester of vinyl acetic acid as shown in Scheme Ic using literature methods or modifications thereof. (D. P. Curran & J. Chao, J. Org. Chem., 1988, 53, 5369-71; J. N. Kim & E. K. Ryu, Heterocycles, 1990, 31, 1693-97) . Scheme Ic Q -S(0)o- 2 , O R= Ph or Et The compounds of the present invention where R 2 or R 3 is e.g. alkoxycarbonyl may be prepared by reacting the free amidines, amines or guanidines with an activated carbonyl derivative, such as an alkyl chloroformate. In compounds of the second embodiment, the conversion of the free amines, amidines and guanidines to such acyl-nitrogen groups may optionally be performed prior to coupling an isoxazoline acetic acid with e.g β-amino acids, as illustrated in Scheme la. The compounds of the present invention wherein Y is an oxyalkoxy group, e.g. alkoxycarbonyloxyalkoxy, may be prepared by reacting a suitably protected carboxylic acid of Formula I with an e.g. an alkoxycarbonyloxyalkyl chloride in the presence of an iodide source, such as tetrabutylammonium iodide or potassium iodide, and an acid scavenger, such as triethylamine or potassium carbonate, using procedures known to those skilled in the art. The appropriately substituted racemic β-amino acids may be purchased commercially or, as is shown in Scheme II, Method 1, prepared from the appropriate aldehyde, malonic acid and ammonium acetate according to the procedure of Johnson and Livak (J . Am. Chem. Soc. 1936, ££., 299) . Racemic β-substituted-β-amino esters may be prepared through the reaction of dialkylcuprates or alkyllithiums with 4-benzoyloxy-2-azetidinone followed by treatment with anhydrous ethanol (Scheme I, Method 2) or by reductive amination of β-keto esters as is described in WO9316038. (Also see Rico et al., J. Org. Chem. 1993, ϋ£, 7948-51.) Enantiomerically pure β- substituted-β-amino acids can be obtained through the optical resolution of the racemic mixture or can be prepared using numerous methods, including: Arndt- Eistert homologation of the corresponding α-amino acids as shown in Scheme II, Method 3 (see Meier, and Zeller, Anσew. Chem. Xnt. F.d. Fnςrl . 1975, 2A, 32; Rodriguez, et al. Tetrahedron Lett. 1990, 21, 5153; Greenlee, -T. Med. Chem. 1985, 2.B., 434 and references cited within) ; and through an enantioselective hydrogenation of a dehydroamino acid as is shown in Scheme II, Method 4 (see Asymmetric Synthesis, Vol. 5, (Morrison, ed.) Academic Press, New York, 1985) . A comprehensive treatise on the preparation of β-amino acid derivatives may be found in patent application WO 9307867, the disclosure of which is hereby incorporated by reference. Srheme X X Method 1 R 4 Xi COJMΘ Method 4 enantiosβlθctive hydrogenation The synthesis of N 2 -substituted diaminopropionic acid derivatives can be carried out via Hoffman rearrangement of a wide variety of asparagine derivatives as described in Synthesis, 266-267, (1981) . The appropriately substituted pyrrolidine-, piperidine- and hexahydroazepineacetic acids may be prepared using a number of methods. The pyrrolidines are conveniently prepared using an Arndt-Eistert homologation of the corresponding proline as shown in Scheme III, Method 1 (see Meier, and Zeller, Anσew. Chem. Int. Ed. Engl. 1975, 14, 32; Rodriguez, et al. Tetrahedron Lett. 1990, 21, 5153; Greenlee, J. Med. Chem. 1985, 2SL, 434 and references cited within) . The piperidines can be prepared by reduction of the corresponding pyridine as shown in Scheme III, Method 2 The hexahydroazepines are prepared by reduction of the corresponding vinylogous amide using sodium cyanoborohydride as depicted in Scheme III, Method 3. Scheme III Method 1 « L , rrvw 1) IBCF. NMM II 1) Ag\ MeOH „ „ _ BocN-^^COzH ■ BocN^_^ CHN — — ► Boc ^- ^ < 2)C tfc ζ CHN * <jf COjMe Method 2 Method 3 Many additional appropriately substituted heterocycles are available commercially or can be readily modified by procedures known by one skilled in the art. Appropriately substituted morpholines can be prepared from amino acids via the sequence of steps depicted in Scheme Ilia, method l(see Brown, et. al. J. Chem. Soc. Perkin Trans I, 1987, 547.; Bettoni, et. al. Tetrahedron 1980, 36, 409. Clarke, F.H. J. Org. Chem. 1962, 27, 3251 and references therein.) N-ethoxycarbonylmethyl-l,2-diazaheterocyles are prepared by condensation of suitably substituted dibromides with benzylhydrazine followed by Mitsunobu reaction with ethyl hydroxyacetate and deprotection as shown in Scheme Ilia, method 2 (see Kornet, et. al. J. Pharm. Sci. 1979, 68, 377.; Barcza, et. al. J. Org. Chem. 1976, 41, 1244 and references therein.) Scheme Ilia Method l Method 2 A general synthetic protocol to the compounds of the first embodiment of this invention is depicted in Scheme IV. Coupling of a suitable Boc-protected amino alcohol to an appropriately substituted phenol under Mitsunobu conditions (see Mitsunobu, Synthesis 1981, 1) is followed by oximation using hydroxylamine hydrochloride in 1:1 ethanol/pyridine. Isoxazoline formation, ester saponification and Boc-deprotection (33% TFA/DCM) then affords the compounds of this invention in good overall yield. The synthesis of the spiro-fused isoxazolinyl imides of the third embodiment of the present invention is exemplified by the general protocol depicted in Scheme V. Dipolar cycloaddition of an oximinoyl chloride with a α-methylene diester affords an isoxazolinyl diester, which is deesterified using the silanolate method. Dehydration to the anhydride according to Ishihara, et al. (Chem. Pharm. Bull. 1992, 4H, 1177-85) followed by imide formation using an appropriately substituted amino ester affords the spirocycle. Alternatively, the imide may be prepared directly from the isoxazoline diester according to Culbertson, et al. (J. Med. Chem. 1990, 22, 2270-75) . Amidine formation or Boc deprotection followed by ester saponification then affords the compounds of this invention in good overall yield. Scheme V The synthesis of the spiro-fused isoxazolinyl amides of the third embodiment of the present invention is exemplified by the general protocol depicted in Scheme VI. Dipolar cycloaddition of an oximinoyl chloride with a α-methylene lactone affords the isoxazolinyl lactone, which is reacted with an appropriate amino ester to afford the amide (see The Chemistry of the Amides (Zabicky, ed.), p 96, Interscience, New York, 1970; Prelog, et al., Helv. Chi . Acta 1959, 42, 1301; Inubushi, et al., J. Chem. Soc. r Chem. Commun. 1972, 1252) . Amidine formation or Boc deprotection followed by ester saponification then affords the compounds of this invention in good overall yield. Sche e VI The synthesis of the spiro-fused isoxazolinyl cycloalkenes of the third embodiment of the present invention is exemplified by the general protocol depicted in Scheme VII. Dipolar cycloaddition of an oximinoyl chloride with an appropriately substituted α- methylene lactone affords the isoxazolinyl lactone. The lactone is then reacted with an appropriate lithium dimethyl alkylphosphonate, followed by PCC oxidation. The resulting diketophosphonate undergoes an intramolecular ittig reaction in the presence of K 2 C03/18-crown-6 according to the method described by Lim and Marquez (Tetrahedron Lett. 1983, 21, 5559) . Amidine formation or Boc deprotection followed by ester saponification then affords the compounds of this invention in good overall yield. Sc e VII or The dipolarophiles used to prepare the compounds of this invention may be prepared by numerous methods. The ω-alkenoic ester class of dipolarophile may be purchased commercially or prepared by oxidation of the corresponding o-alkenols by the method of Corey and Schmidt (Tetrahedron Lett. 1979, 399, Scheme VIII, Method 1) . The o-methylene diester and α-methylene lactone class of dipolarophile may be purchased commercially or can be prepared by numerous methods from the corresponding diester (see Osbond, J. Chem. Soc. 1951, 3464; Ames and Davey, J. Chem. Soc. 1958, 1794; Vig, et al., Ind. J. Chem. 1968, £., 60; Grieco and Hiroi, . Chem. Soc. P Chem. Commun. 1972, 1317, Scheme VIII, Method 2). The 3-(styryl)propionic ester class of dipolarophile may be prepared by palladium-catalyzed cross coupling of the appropriately substituted bromo- or iodohydrocinnamic acid to a vinylmetal species according to methods cited within Mitchell (Synthesis 1992, 803) and Stille tAngew . Chem. Tni- . Ed. Engl. 1986, 22, 508, Scheme VIII, Method 3) . Scheme VTTT Method 1 Method 2 MeO.C— ^ COaMβ ~^- Me0 2 C^— C ^ Mβ Method 3 Compounds of formula I wherein b is a double bond can be prepared using one of the routes depicted in Scheme IX. Bromination followed by subsequent dehydrobromination of a suitably substituted methyl 3- (cyanophenyl)isoxazolin-5-ylacetate, prepared as described above, using the method of Ξlkasaby & Salem (Indian J. Chem., 1980, 19B, 571-575) provides the corresponding isoxazole intermediate. Alternately, this intermediate can be obtained by 1,3-dipolar cycloaddition of a cyanophenylnitrile oxide (prepared from the corresponding chlorooxime as described in Scheme I) with an appropriate alkyne to give the isoxazole directly. Hydrolysis of the ester using conventional methods known to one skilled in the art of organic synthesis gives the acetic acids. Coupling of the resulting acids to an appropriately substituted a- or β-amino ester using standard coupling reagents, such as TBTU, affords a nitrile-amide. The nitrile is then converted to the amidine via the imidate or thioimidate under standard conditions to give the prodrug esters. Saponification gives the acids. Scheme IX Compounds of Formula I wherein R 1 is (R 2 ) (R 3 ) N (R 2 N=) CN (R 2 ) - and V is phenylene are prepared as illustrated in Scheme X . Cycloaddition of an appropriately N-protected aminophenylaldoxime with vinyl acetic acid, t-butyl ester, using the conditions described above provides t-butyl [3- (4-t- butyloxycarbonylaminophenyl) isoxazolin-5-yl] acetate . Hydrolysis of the ester with lithium hydroxide provides the free acid which can be coupled with a suitably substituted methyl 3-aminopropionate as previously described . After deprotection, the aniline is converted to the corresponding guanidine using the method described by Kim et al . (Tetrahedron Lett . , 1993 , 48 , 7677 ) . A final deprotection step to remove the BOC groups provides guanidino compounds of Formula I . Scheme X BOC TBTU/Et 3 N EtOAc or DMF The compounds of this invention and their preparation can be further understood by the following procedures and examples, which exemplify but do not constitute a limit of their invention. Example 1 3- T4- (2-Piperidin-4-yl) ethoxyphenyl!- ( 5R. S) -isoxazolin- 5-ylacetic Acid. Trifluoroacetic Acid Salt Part A. Preparation of 7- (4-W-t-B._tylnxvcarhor_y1piperi- dinvlMethanol This material was prepared from 4-piperidine-2- ethanol according to European Patent Application Publication Number 478363 A2. Part B. 4-f (2-Ar- -B_3ty1oyycarhr>ny1piperidin-4-yl eth- oxvlbenzaldehyde To a solution of 2- (4-N-t-Butyloxycarbonylpiperi- dinyl)ethanol (7.71 g, 33.6 mmol), 4-hydroxybenzaldehyde (4.11 g, 33.6 mmol) and PPh 3 (8.82 g, 33.6 mmol) in THF (60 mL) at -20 'C was added a solution of DEAD (5.3 mL, 33.7 mmol) in THF (30 mL) over 2 hours. During the addition, a deep red solution resulted, which changed to a golden color upon warming to room temperature overnight (18 hours) . At this time the solution was concentrated and redissolved in EtOAc. It was then washed with water, 0.1ΛT HC1, IM NaOH, sat. NaCl and dried (MgSθ 4 ) . Concentration gave a solid (-20 g) , which was purified using flash chromatography (10-20-30- 40-50% EtOAc/hexanes step gradient), affording 7.82 g (70%) of the desired ether after pumping to constant weight; mp 76.4-79.7 'C; *H NMR (300 MHz, CDCI3) δ 9.88 (s IH) , 7.83 (d, J = 8.4 Hz, 2H) , 6.98 (d, J = 8.4 Hz, 2H) , 4.10 (bd, J = 12.8 Hz, 2H) , 4.04 (t, J = 6.6 Hz 2H), 2.69 (bt, 2H), 1.84 (m, 2H) , 1.70 (bd J = 14.3 Hz, 2H) , 1.46 (s, 9H, overlapped with m, 2H) , 1.10 (m, 2H) . Part C . 4- f (2-A7- -B_:ιtyl oxycarbony1 pi peridin-4-yl i eth¬ oxy 1 benzaldoxime To a solution of 4- [ (2-N-t-butyloxycarbonylpiperi- din-4-yl) ethoxy] benzaldehyde (3 .16 g, 9 . 48 mmol) in MeOH (20 mL) was added hydroxylamine hydrochloride (1.27 g, 18.3 mmol) and 2M NaOH (7 mL, 14 mmol) . The resulting suspension was stirred overnight at room temperature (18 hours) . The mixture was brought to pH 4 using IM HCI, followed by filtration and water wash. The crystals were dried under vacuum over P 2 O 5 , affording 2.88 g (87%); mp: 114.4-116.1 * C; *H NMR (300 MHz, CDCI 3 ) δ 8.09 (s, 2H), 7.51 (d, J = 8.8 Hz, 2H) , 6.89 (d, J = 8.8 Hz, 2H), 4.10 (b, 2H), 4.03 (t, J = 6.2 Hz 2H) , 2.71 (bt, 2H), 1.73 (m, 4H) , 1.46 (s, 9H) , 1.19 (m, 2H) . Part D. 4-T (2-N-t-Butvloxvcarbonylpiperidin-4-vl )eth¬ oxyIbenzaldoximinoyl Chloride To a solution of 4-[ (2-N-t-butyloxycarbonylpiperi- din-4-yl)ethoxy]benzaldoxime (955 mg, 2.74 mmol) in DMF (5 mL) was added ΝCS (366 mg, 2.74 mmol) in 3 portions. After 3 hours, the solution was diluted with EtOAc and washed with water, sat. ΝaCl, dried (MgS0 4 ) and concentrated. The resulting solid was crystallized from ether/hexanes to give 548 mg (52%) of the oximinoyl chloride; mp: 119.3-119.9 * C; X H ΝMR (300 MHz, CDCI 3 ) δ 8.37 (bs IH), 7.77 (d, J = 8.8 Hz, 2H) , 6.88 (d, J = 8.8 Hz, 2H), 4.12 (bd, J = 13.2 Hz, 2H) , 4.04 (t, J = 6.2 Hz 2H), 2.72 (bt, J = 12.1 Hz, 2H) , 1.70 (m, 5H) , 1.46 (s, 9H), 1.10 (m, 2H) . Part E. Methyl 3—T4—f (2-N-t-Bυ _ylPxycarfrony_lpiperid i.n-4- yl)ethoxyIphenyll- (5R, S)-isoxazolin-S-ylacetate To a solution of 4-[ (2-N-t-butyloxycarbonylpiperi- din-4-yl)ethoxyIbenzaldoximinoyl chloride (400 mg, 1.045 mmol) and methyl 3-butenoate (200 mg, 2.00 mmol) was added TEA (0.15 mL, 1.1 mmol) . The resulting suspension was heated at reflux for 5 hours, cooled to room temperature and diluted with EtOAc. It was then washed with 0.1M HC1, water, sat. NaCl, dried (MgSO_ι) and concentrated. The resulting solid was crystallized from DCM/hexanes to give 357 mg (77%) of the isoxazoline; mp: 139.1-140.9 * C; *H NMR (300 MHz, CDCI3) δ 7.59 (d, J = 8.8 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H) , 5.08 (m, IH) , 4.10 (bd, J = 13.2 Hz, 2H) , 4.04 (t, J = 5.9 Hz 2H) , 3.73 (s, 3H), 3.53 (dd, J = 16.5, 10.1 Hz, IH) , 3.10 (dd, J = 16.8, 7.1 Hz, IH) , 2.88 (dd, J = 16.1, 5.9 Hz, IH), 2.71 (bt, J = 12.8 Hz, 2H) , 2.64 (dd, J = 15.8, 7.7 Hz, IH), 1.72 (m, 5H) , 1.46 (s, 9H) , 1.08 (m, 2H) . Part F. 3- \ .~ \ f2-tt-t-Buf_ylpχycarbQny]piperid_Ln-4,- yl)ethoxy}phenyl]-(5fl_.,5)-isnxazQlin-5-y_lacetic Acid To a solution of methyl 3- [4-{ (2-N-t-butyloxycar- bonylpiperidin-4-yl)ethoxyJphenyl]- (5.R, S)-isoxazolin-5- ylacetate (47 mg, 0.105 mmol) in THF (2 mL) was added 0.5M LiOH (1 mL, 0.5 mmol) . The reaction was stirred at room temperature for 5 hours, then was acidified to pH 3 using 0. IM HCI. The mixture was washed with DCM and the combined organic fraction dried (MgS0 4 ) and concentrated. The resulting solid was crystallized from EtOAc/hexanes to give 34 mg (74%) of the carboxylic acid; mp: 169.1-170.6 'C; X H NMR (300 MHz, CDCI3) δ 1 .60 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 8.8 Hz, 2H) , 5.10 (m, IH) , 4.08 (bd, 2H, overlapped with t, J = 5.9 Hz 2H) , 3.55 (dd, J = 16.5, 10.2 Hz, IH) , 3.11 (dd, J = 16.8, 7.0 Hz, IH) , 2.93 (dd, J = 16.1, 6.2 Hz, IH) , 2.71 (m, 3H), 2.00 (m, 2H), 1.72 (m, 5H) , 1.46 (s, 9H) . Part G. 3- T4- (2-Piperidin-4-yl) thoxyphenyl1- ( R. S) - isoxa olin-'-ylacetic Acid. Trif1noroace ic Acid Salt To a solution of 3- [4-{ (2-N-t-Butyloxycarbonylpi- peridin-4-yl)ethoxy}phenyl]- (5R, S)-isoxazolin-5-ylacetic acid (53 mg, 0.12 mmol) in DCM (2 mL) was added TFA (1 mL, 13 mmol) . After 1.5 hours, the product was crystallized by the addition of ether, affording 33 mg (60%) of the amino acid; mp: 142.4-143.1 * C; 1 H NMR (300 MHz, CDC1 3 ) δ 7.59 (dd, J = 8.8, 2.6 Hz, 2H) , 6.96 (dd, J = 8.8, 2.6 Hz, 2H) , 5.03 (m, IH) , 4.10 (m, 2H) , 3.55 (ddd, J = 16.8, 10.3, 2.2 Hz, IH) , 3.38 (bd, J = 12.4 Hz, 2H) , 3.16 (ddd, J = 17.2, 7.7, 2.2 Hz, IH) , 2.98 (bt, J = 13.2 Hz, 2H) , 2.69 (m, 2H) , 2.01 (bd, J = 14.3 Hz, 2H) , 1.91 (m, IH) , 1.80 (m, 2H) , 1.46 (m, 2H) . Example 4 (2.?)-(5fl,.?)-.3-f4-f (2-Piperitiin-4-yl)et oxyϊphenyllisox- azolin-5-yl( r (benzyloxy) carbonyl!amino11acetate, Trifluprpace ic Acid Salt Part A. Benzyl L-2- f r (Benzyloxy. carbonyl 1amino!-3- butenoate This material was prepared from N-Cbz-L-glutamic acid ot-benzyl ester according to Krol, et al . ( . Or . CiiSS 1991, 728) . Part B. Benzvl ( 2S) - ( SR. S) - l 3- \ 4- i ( 2-N-/:-Butγloxycarhon- ylpiperidin-4-yl)ethPxy}phenyl1ispχazplin-5-yl{ r (benzyl- oxy) carbonyl!amino11acetate To a solution of 4- [ (2-N-t-butyloxycarbonylpiperi- din-4-yl)ethoxy]benzaldoxime (852 mg, 2.44 mmol) and benzyl L-2- [[ (benzyloxy) carbonyl]amino]-3-butenoate (612 mg, 1.88 mmol) in DCM (10 mL) was added 5% NaOCl (common household bleach, 4 mL, 2.8 mmol) . The mixture was rapidly stirred at room temperature for 22 hours, after which time it was diluted with water and DCM. After separation of the layers, the aqueous was washed with DCM (3x) . The combined organic extracts were dried (MgSθ 4 ) and concentrated in vacuo, giving 1.4 g. Purification using flash chromatography (10% EtOAc/hexanes - 30% EtOAc/hexanes) then afforded 886 mg (70%) of an oily product as a 2.5 : 1 mixture of the erythro and threo isomers; 1 H NMR (400 MHz, CDCI3) δ 7.50 (m, 2H) , 7.34 (m, 5H) , 7.23 (m, 5H) , 6.87 (d, J = 8.8 Hz, 2H) , 5.47 (bd, IH) , 5.12 (m, 5H) , 4.60 (m, IH) , 4.07 (m, overlapped with 4.03 (t, J = 6.1 Hz, 4H) ) , 3.36 (m, 2H) , 2.71 (bt, J = 12.7 Hz, 2H) , 1.70 (m, 5H) , 1.45 (s, 9H) , 1.18 (m, 2H) ; Anal. Calc. for C3 8 H 45 N3O8: C, 67.93; H, 6.76; N, 6.26. Found: C, 67.95; H, 6.77; N, 6.17. Part C. l?.S) - ( ,R. S) - \3- ^- i (?-/V-?_-Bπty!oxycarbonyl iper- idin-4-yl . ethoxyIphenyl1 isoxay.olin-5-γl f r (benzvloxy) car¬ bonyl!amino!1acetic Acid A solution of benzyl (2S)- (5JR,5)- [3- [4-{ (2-N-t- butyloxycarbonylpiperidin-4-yl)ethoxyJphenyl]isoxazolin- 5-yl{ [ (benzyl-oxy) carbonyl]amino} ]acetate (875 mg, 1.302 mmol) in THF (5 mL) was saponified over 5 hours using 0.5Λf LiOH (3.5 mL) according to Example 1, Part F. To the crude product was added methanol, causing crystallization of one of the diastereomers. Filtration and pumping to constant weight gave 295 mg (39%); mp: 216.1 * C; !H NMR (400 MHz, DMSO-dε, 80 * C) δ 7.50 (d, J = 8.9 Hz, 2H) , 7.23 (s, 5H) , 6.96 (d, J = 8.9 Hz, 2H) , 6.17 (bs, IH), 4.99 (m, 3H) , 4.07 (t, J = 6.1 Hz, 2H) , 3.90 (m, 3H) , 3.35 (d, J = 9.3 Hz, 2H) , 2.72 (bt, J = 12.4 Hz, 2H), 1.67 (m, 5H) , 1.39 (s, 9H) , 1.08 (m, 2H) . The filtrate was concentrated in vacuo and pumped until constant weight was achieved, giving 200 mg (26%) of the carboxylic acids as a mixture of erythro- and threo- isomers; TLC (silica gel 60, 20% MeOH/CHCl 3 ) R f = 0.23, Mass Spectrum (ESI, e/z, relative abundance) 582 (M + H) + , 32%; 526 (M - C 4 H9 + H2) + , 100%; 482 (M - Boc + H 2 ) + , 91%) . Part D. (2S)- (5ft. S)-r3-r4-f(?-Pi eridin-4-γl)ethox- ylphenyllisoxazolin-5-ylf r (benzyloxy) carbonyl! mino! 1a- cetic Acid (isomer A) (2S)- (5R, S) - [3- [4-{ (2-N-t-Butyloxycarbonylpiperi- din-4-yl)ethoxy}phenyl] isoxazolin-5-yl{ [ (benzyloxy) car- bonyl]amino}]acetic acid (23 mg, 0.039 mmol) was Boc- deprotected using 33% TFA/DCM according to Example 1, Part G, giving 15 mg (79%); mp: 302 * C (dec); 1 H NMR (400 MHz, DMSO-d6, 60 * C) δ 7.57 (d, J = 8.8 Hz, 2H) , 7.30 (s, 5H), 6.99 (d, J = 8.8 Hz, 2H) , 5.05 (s, 2H, coincident with m, IH) , 4.35 (d, J = 4.9 Hz, IH) , 4.09 (t, J = 6.1 Hz, 2H) , 3.52 (dd, J = 17.3, 10.7 Hz, IH) , 3.26 (m, 3H), 2.88 (dt, J = 12.7, 2.7 Hz, 2H) , 1.88 (bd, J = 14.4 Hz, 2H) , 1.80 (m, IH) , 1.72 (m, 2H) , 1.38 (m, 2H) . Part D'. j2S)- (5R, S)-f3-_4-f (2-Piperidin-4-yl)ethox- ylphenyllisoxazolin-5-ylf r (benzyloxy) carbonyl1amino! 1a- cetic Acid. Trifl prpacetic Acid Salt (iscmer B) (2S)- (5R, S) - [3- [4-{ (2-N-t-Butyloxycarbonylpiperi- din-4-yl)ethoxyJphenyl]isoxazolin-5-yl{ [ (benzyloxy)car¬ bonyl]amino}]acetic acid (177 mg, 0.304 mmol) was Boc- deprotected using 33% TFA/DCM according to Example 1, Part G, giving 3 mg (2%) of the TFA salt; mp: >400 "C; i H NMR (400 MHz, DMSO-d 6 , 60 * C) δ 8.48 (bs, 0.5H), 8.15 (bs, 0.5H), 7.55 (d, J = 8.9 Hz, 2H) , 7.30 (m, 5H) , 6.97 (d, J = 8.9 Hz, 2H) , 5.05 (s, 2H) , 4.96 (m, IH) , 4.33 (m, IH) , 4.07 (t, J = 6.3 Hz, 2H) , 3.38 (m, 2H) , 3.26 (bd, J = 12.0 Hz, 2H), 2.87 (m, 2H) , 1.86 (bd, J = 14.2 Hz, 2H) , 1.78 (m, IH) , 1.70 (apparent q, J = 6.3 Hz, 2H) , 1.36 (bq, J = 13.2 Hz, 2H) . Example 6 3-(3- [ .-(Piperidin-4-ylmethoxy)phenyl1-(5fl,5)-ispxazpl- in-5-yl)prppipnic Acid, Trifluprpacetic Acid Salt Part A. Ethyl N-t-Butylpχycarbpnylpiperidin -4- carbpxylate To a stirred solution of ethyl isonipecotate (20.01 g, 0.1273 mol) in EtOAc (100 mL) at 0 * C was added dropwise a solution of B0C 2 O (27.76 g, 0.1272 mol) in EtOAc (50 mL) . The mixture was allowed to warm to room temperature overnight. After 20 hours, the mixture was washed with water, O.lΛ HCI, sat. NaHCθ3, sat. NaCl and dried (MgSθ 4 ) • Concentration and pumping under vacuum to constant weight gave 32.54 g (99%) of the desired carbamate as a mobile oil; l -H NMR (300 MHz, CDCI3) δ 4.13 (q, J = 7.0 Hz, 2H) , 4.03 (dm, J = 13.6 Hz 2H) , 2.81 (m, 2H) , 2.41 (m, IH) , 1.86 (dm, J = 13.6 Hz, 2H) , 1.62 (m, 2H) , 1.44 (s, 9H) , 1.24 (t, J = 7.0 Hz, 3H) . Part B. N-t-Butvloxycarbonvlpiperid n-4-γ. methanol To a solution of ethyl N-t-butyloxycarbonylpiperi- dine-4-carboxylate (32.34 g, 0.1257 mol) in THF (100 mL) at 0 * C was added dropwise lΛ LAH in THF (87.9 mL, 0.0879 mol) . After 2 hours, excess hydride was quenched by the addition of water (3.2 mL) , 2M NaOH (3.2 mL) and water (10 mL) . The mixture was filtered, washed with EtOAc and the filtrate washed with water, sat. NaCl, dried (MgSθ 4 ) and concentrated. Pumping to constant weight gave 22.72 g (84%); mp: 79.2-81.1 "C; λ H NMR (300 MHz, CDCI3) δ 4.12 (bd, J = 12.8 Hz 2H) , 3.49 (d, J = 6.2 Hz, 2H) , 2.68 (dt, J = 13.2, 1.8 Hz, 2H) , 1.69 (m, 3H) , 1.44 (s, 9H, overlapped with m, IH) , 1.14 (m, 2H) . Part C. 4- (N-t-Butvloxvcarbonγlpiperidin-4-vlmethoxv)- benzaldehyde To N-t-butyloxycarbonylpiperidin-4-ylmethanol (7.87 g, 36.5 mmol), p-hydroxybenzaldehyde (4.46 g, 36.5 mmol) and PPh 3 (9.59 g, 36.5 mmol) in THF (100 mL) at -20 * C was added DEAD (5.75 L, 36.5 mmol) in THF (50 mL) according to Example 1, Part B, affording 8.14 g (70%); mp: 115.6-116.8 "C; λ H ΝMR (300 MHz, CDCI3) δ 9.86 (s, IH) , 7.81 (d, J - 8.8 Hz, 2H) , 6.96 (d, J = 8.8 Hz, 2H) , 4.15 (bd, J = 13.2 Hz 2H) , 3.87 (d, J = 6.6 Hz, 2H) , 2 . 74 (dt , J - 12 . 4 , 1 . 8 Hz , 2H) , 1 . 97 (m, IH) , 1 . 81 (bd, J = 12 . 8 Hz , 2H) , 1 . 45 (s , 9H) , 1 . 27 (dq, J = 12 . 1 , 4 . 0 Hz , 2H) . Part D. 4- (N-t-Butvloxvcarbonvlpiperidin-4-vlmethoxv)- benzaldoxime A mixture of 4- (N-t-butyloxycarbonylpiperidin-4- ylmethoxy)benzaldehyde (3.16 g, 9.89 mmol) and hydroxylamine hydrochloride (1.27 g, 18.3 mmol) in 9:1 MeOH/pyridine (30 mL) was heated at reflux for 18 hours. The mixture was cooled to room temperature and concentrated to dryness . The residue was dissolved in EtOAc and washed with O.lΛf HCI (3x) , water, sat. CuS0 4 (2x) , water, sat. ΝaCl, dried (MgS0 4 ) and concentrated, giving 3.19 g (96%) of the oxime; mp: 140.1-141.8 'C; i H ΝMR (300 MHz, CDCI3) δ 8.07 (s, IH) , 7.48 (d, J = 8.8 Hz, 2H) , 6.86 (d, J = 8.8 Hz, 2H) , 4.14 (bs, 2H) , 3.80 (d, J = 6.2 Hz, 2H) , 2.71 (bt, J = 12.4 Hz, 2H) , 1.95 (m, IH) , 1.80 (bd, J = 12.4 Hz, 2H) , 1.45 (s, 9H) , 1.26 (m, 2H) . Part E. 4- (N-t-Butyloxycarbonylpiperidin-4-ylmethoxy) - benzaldoximinoyl Chloride 4- (N-t-Butyloxycarbonylpiperidin-4-ylmethoxy)- benzaldoxime (3.19 g, 9.54 mmol) in DMF (10 mL) was reacted with ΝCS (1.27 g, 9.51 mmol) for 18 hours according to Example 1, Part D to afford the hydroximinoyl chloride (1.17 g, 33%); mp: 178.0-179.8 * C; ^-H ΝMR (300 MHz, CDCI 3 ) δ 7.75 (d, J = 9.0 Hz, 2H) , 6.86 (d, J = 9.0 Hz, 2H) , 4.17 (bd, J = 12.4 Hz, 2H) , 3.80 (d, J = 6.2 Hz, 2H) , 2.74 (dt, J = 12.8, 1.8 Hz, 2H) , 1.95 (m, IH) , 1.81 (bd, J = 12.1 Hz, 2H) , 1.46 (s, 9H) , 1.27 (dq, J = 12.5, 4.0 Hz, 2H) . Part F. Methvl 3- (3- T4- (JV- -Bntyloxycarbonylpiperidin-4- ylmethoxy)phenyl1- (5R, S)-isoxazolin-5-yl )propionate 4- (N-t-Butyloxycarbonylpiperidin-4-ylmethoxy)benz- aldoximinoyl chloride (738 mg, 2.00 mmol), methyl 4- pentenoate (230 mg, 2.02 mmol) and TEA (0.28 mL, 2.0 mmol) were heated at reflux for 1 hour according to Example 1, Part E. Crystallization from ether/hexanes afforded 537 mg (60%) . mp: 97.9-99.9 * C; X H NMR (300 MHz, CDCI3) δ 7.57 (d, J = 9.0 Hz, 2H) , 6.87 (d, J = 9.0 Hz,2H), 4.74 (m, IH) , 4.15 (bd, J = 13.2 Hz, 2H) , 3.81 (d, J = 6.2 Hz, 2H), 3.67 (s, 3H) , 3.40 (dd, J = 16.5, 10.2 Hz, IH) , 2.95 (dd, J = 16.5, 7.3 Hz, IH) , 2.73 (dt, J = 13.2, 1.1 Hz, 2H) , 2.52 (t, J = 7.3 Hz, 2H) , 1.98 (q, J = 7.0 Hz, 2H, overlapping m, IH) , 1.81 (bd, J = 12.8 Hz, 2H), 1.45 (s, 9H) , 1.26 (dq, J = 12.4, 3.7 Hz, 2H) . Part G. 3- (3- 14- (N-t-Butγloxycarbonylpiperidi n-4-ylmeth- oxv)phenvl1-(5ft.-9)-isoxazolin-5-yl )propi nic Acid Methyl 3-(3- [4- (N-t-butyloxycarbonylpiperidin-4- ylmethoxy)phenyl]- (5.R, S)-isoxazolin-5-yl)propionate (250 mg, 0.560 mmol) was saponified using 0.5Λ LiOH (2 mL, 1 mmol) in THF (2 mL) . The reaction was stirred at room temperature for 3 hours, according to Example 1, Part F. The resulting solid was crystallized from DCM/hexanes to give 163 mg (67%) of the carboxylic acid; mp: 146.5- 147.7 * C; i H ΝMR (300 MHz, CDCI3) δ 7.57 (d, J » 8.8 Hz, 2H) , 6.88 (d, J = 8.8 Hz, 2H) , 4.75 (m, IH) , 3.81 (d, J = 6.2 Hz, 2H) , 3.41 (dd, J » 16.5, 10.3 Hz, IH) , 2.95 (dd, J = 16.5, 7.3 Hz, IH) , 2.75 (bt, J = 12.4 Hz, 2H) , 2.57 (t, J = 7.3 Hz, 2H), 1.97 (m, 3H) , 1.81 (bd, J = 12.1 Hz, 2H) , 1.45 (s, 9H) , 1.24 (m, 2H) . Part H. 3- (3- \ 4- (Piperidin-4-γlmethoxy)phenyl !- (5ft.£ - isoxazolin-5-yl)propionic Acid r Trifluoroacetic Acid Sal 3- (3- [4- (N-t-Butyloxycarbonylpiperidin-4-ylmethox- y)phenyl]- (5ft, S)-isoxazolin-5-yl)propionic acid (103 mg, 0.238 mmol) was Boc-deprotected using 33% TFA/DCM according to Example 1, Part G, giving 88 mg (83%) of the TFA salt; mp: 179.1-181.8 * C; i H NMR (400 MHz, MeOH- d 4 ) δ 7.60 (d, J = 9.0 Hz, 2H) , 6.97 (d, J = 9.0 Hz, 2H) , 4.73 ( , IH), 3.94 (d, J = 6.1 Hz, 2H) , 3.46 (m, 3H) , 3.06 (m, 3H) , 2.45 (dt, J - 7.3, 1.2 Hz, 2H) , 2.16 (m, IH) , 2.08 (bd, J = 15.4 Hz, 2H) , 1.94 (q, J = 6.6 Hz, IH) , 1.64 (dq, J = 14.2, 4.2 Hz, 2H) . Example 7 3- \4-(Piperidin-4-ylmethoxy)phenyl1-(5ft, S)-isoxazolin-5- vlacetic Acid. Trifluoroacetic Acid Salt Part A. Methyl 3- T4- (At- -Butyloxycarbonyl iperidin-4- ylmethoxv)phenvl!- (5ft. <?)-isoxazol in-5-ylacetate 4- (N-t-Butyloxycarbonylpiperidin-4-ylmethoxy)benz- aldoximinoyl chloride (412 mg, 1.12 mmol), methyl 3- butenoate (200 mg, 2.00 mmol) and TEA (0.18 mL, 1.3 mmol) were heated at reflux for 2 hours according to Example 1, Part E. Crystallization from chloroform/cyclohexane afforded 329 mg (68%) . mp: 97.9- 99.9 * C; X H NMR (300 MHz, CDCI3) δ 7.58 (d, J = 8.8 Hz, 2H) , 6.88 (d, J = 8.8 Hz,2H), 5.04 (m, IH) , 4.15 (bd, J = 13.2 Hz, 2H), 3.81 (d, J = 6.2 Hz, 2H) , 3.71 (s, 3H) , 3.54 (dd, J = 16.8, 10.3 Hz, IH) , 3.08 (dd, J = 16.8, 7.3 Hz, IH) , 2.86 (dd, J = 16.1, 5.9 Hz, IH) , 2.73 (dt, J = 12.8, 1.8 Hz, 2H) , 2.62 (dd, J = 15.8, 7.7 Hz, IH) , 1 . 95 (m, IH) , 1 . 81 (bd, J = 13 . 2 Hz , 2H) , 1 . 45 ( s , 9H) , 1 . 25 (dq, J = 12 . 8 , 4 . 4 Hz , 2H) . Part B. 3- \ 4- (Λt-t-Butvloxγcarbonvlpiperidi.n-4-vlmeth- oxv)phenyl1- (5ft..?) -isoxazol i n-5-ylaceti c Acid Methyl 3-[4- (N-t-butyloxycarbonylpiperidin-4- ylmethoxy)phenyl]- (5ft,S)-isoxazolin-5-ylacetate (329 mg, 0.762 mmol) was saponified using 0.5M LiOH (3 mL, 1.5 mmol) in THF (5 mL) . The reaction was stirred at reflux for 4 hours, according to Example 1, Part F to give 72 mg (22%) of the carboxylic acid; mp: 164.0-164.8 "C; X H NMR (300 MHz, CDCI3) δ 7.58 (d, J = 8.8 Hz, 2H) , 6.88 (d, J = 8.8 Hz, 2H) , 5.07 (m, IH) , 4.15 (bd, J = 13.6 Hz, 2H) , 3.82 (d, J = 6.2 Hz, 2H) , 3.53 (dd, J = 16.8, 10.3 Hz, IH) , 3.10 (dd, J = 16.8, 7.0 Hz, IH) , 2.91 (dd, J = 16.1, 5.9 Hz, IH) , 2.73 (dt, J = 14.6, 1.8 Hz, 2H) , 2.68 (dd, J = 16.1, 7.3 Hz, IH) , 1.97 (m, IH) , 1.81 (bd, J = 13.2 Hz, 2H), 1.45 (s, 9H) , 1.26 (dq, J = 12.8, 4.4 Hz, 2H) . Part C. 3- T4- (Piperidin-4-γlmethoxy)phenyl 1- (5ft. £ - isoxazolin-5-γlacetic Acid. Tri fluoroace i c Acid Salt 3- [4- (N-t-Butyloxycarbonylpiperidin-4-ylmethox- y)phenyl]- (5ft,S)-isoxazolin-5-ylacetic acid (72 mg, 0.172 mmol) was Boc-deprotected using 33% TFA/DCM according to Example 1, Part G, giving 64 mg (94%) of the TFA salt; mp: 220 * C (dec); X H ΝMR (300 MHz, MeOH- d 4 ) δ 7.61 (d, J = 9.2 Hz, 2H) , 6.97 (d, J = 9.2 Hz, 2H) , 5.04 (m, IH), 3.95 (d, J = 5.9 Hz, 2H) , 3.56 (dd, J = 17.2, 10.2 Hz, IH) , 3.45 (bd, J = 12.8 Hz, 2H) , 3.18 (dd, J = 17.2, 7.3 Hz, IH) , 3.04 (dt, J = 10.2, 2.9 Hz, 2H) , 2.69 (m, 2H) , 2.18 (m, IH) , 2.08 (bd, J = 14.6 Hz, 2H) 1.63 (bq, 2H) . Exa ple 8 3- 14- (2-Piperidin-4-yl) ethoxyphenyl1- (5ft..<?) -i soxazolin- 5-ylprppipnic Acid, Trifluprpacetic Acid Salt This material was prepared analogously to Example 1, giving the desired material; mp: 114.8-115.7 ' C; 1 H NMR (300 MHz, CD3OD) 57.59 (d, J = 8.4 Hz, 2H) , 6.95 (d, J = 8.4 Hz, 2H) , 4.72 ( , IH) , 4.07 (t, J = 5.9 Hz, 2H) , 3.47 (dd, J = 16.8. 10.2 Hz, IH) , 3.37 (dd, J = 16.8, 7.7 Hz, IH) , 2.98 (m, 2H) , 2.44 (t, J = 7.3 Hz, 2H) , 2.01 (bd, J = 15.0 Hz, 2H) , 1.93 (m, 3H) , 1.80 (m, 2H) , 1.44 (m, 2H) . Example 9 erythro- and- threo-3- 3- - (piperidin-4- yl)methpxylphenyllispχazplin-5- ylf rbutanesulfonyllaminolpropionate, Trifluoroacetic Acid Salt Part A. Dicyclohexylammonium n.L-2-r (Bυtanesulfonyl)- aminpl-4-pentenpic acid To a suspension of D,L-2-amino-4-pentenoic acid (2.54 g, 22.06 mmol) in acetonitrile (35 mL) was added BSTFA (7.3 mL, 27.5 mmol) . The suspension was heated at 55 "C for 2 hours, after which time a golden yellow solution resulted. To this solution was added pyridine (2.2 mL, 27.2 mmol) and n-butanesulfonyl chloride (3.0 mL, 23.1 mmol) . The mixture was heated at 70 "C for 20 hours, then cooled to room temperature. Concentration in vacuo afforded a brown oil, to which was added 15% KHSO 4 (5 mL) . The mixture was stirred for 1 hour and shaken with EtOAc (3x) . The combined organic extracts were washed with sat. NaCl, dried (MgSθ 4 ) , concentrated and the resulting oil dissolved in ether (5 mL) . To this solution was added DCHA (4.38 mL, 22.0 mmol), causing immediate precipitation of the dicyclohexylam¬ monium salt. The solid was collected by filtration and pumped to constant weight, giving 8.42 g (92%); mp: 207.1-208.6 * C; 2 H NMR (400 MHz, MeOH-d 4 ) δ 5.84 (m, IH) , 5.09 (dm, J - 17.1 Hz, IH) , 5.04 (dm, J = 10.2 Hz, IH) , 3.80 (dd, J = 7.1, 5.1 Hz, IH) , 3.18 ( , 2H) , 3.02 (m, 2H) , 2.49 (m, 2H) , 2.06 (m, 4H) , 1.78 (m, 8H) , 1.55 (m, 12H) , 0.94 (t, J = 7.3 Hz) . Part B. Methyl p.τ.-2-r (Butanes._1 onyl )amino!-4-pentenoate To a solution of dicyclohexylammonium D,L-2- [ (butanesulfonyl)amino]-4-pentenoate (8.36 g, 20.07 mmol) in MeOH (50 mL) was added HCl-saturated MeOH (50 mL) . The resulting suspension was stirred at room temperature for 18 hours, diluted with ether, and filtered. Concentration of the filtrate in vacuo was followed by the addition of ether, a second filtration, and washing of the filtrate with O.lM HCl, sat. NaHCθ3, sat. NaCl. The solution was dried over anhydrous MgS0 4 , concentrated and placed under vacuum until constant weight to give 4.49 g (90%) of the desired ester as a light brown oil; i H NMR (300 MHz, CDCI3) δ 5.68 (m, IH) , 5.19 (bd, J - 1.5 Hz, IH) , 5.15 (m, IH) , 4.78 (bd, J = 8.4 Hz, IH), 4.20 (dt, J = 8.8, 5.8 Hz, IH) , 3.77 (s, 3H) , 2.99 (m, 2H) , 2.54 (t, J = 6.6 Hz, 2H) , 1.76 (m, 2H), 1.42 (sextuplet, J = 7.3 Hz, 2H) , 0.93 (t, J = 7.3 Hz, 3H) . Part C. Methyl erythro- and-fchreo-3- (3- .4-1 (Butvloxvcar- bonylpiperidin-4-yl)methoxylphenyllisoxazolin-5- ylf rhutanesulfonyl 1amino!)propionate To a solution of 4-[ (N-t-butyloxycarbonylpiperi- din-4-yl)methoxy]benzaldoxime (2.680 g, 8.01 mmol), methyl D, -2- [ (butanesulfonyl)amino]-4-pentenoate (2.000 g, 8.02 mmol) and TEA (0.11 mL, 0.79 mmol) in THF (10 mL) was added a 5% solution of NaOCl (common household bleach, 15 mL, 10.5 mmol) . The resulting mixture was rapidly stirred at room temperature for 20 hours. The mixture was diluted with EtOAc and water and the layers were separated. The aqueous portion was washed with EtOAc, and the combined organic fraction washed with sat. NaCl and dried over MgSθ 4 .Concentration in vacuo afforded a light brown oil (4.8 g) , which was purified using flash chromatography (0-50% EtOAc/hexanes in 5 steps), giving four components. The least polar of these materials (fractions 8-11) was determined by i H NMR to be the starting olefin (1.520 g, 76%) . The next component isolated in order of increasing polarity (fractions 12-15) was determined by X H NMR to be the starting oxime (1.423 g, 53%) . The next component off of the column (fraction 20) was determined to be the faster of the two diastereomers (317 mg) . This material had co-eluted with an impurity having a i H NMR profile similar to the starting oxime and appeared to be approximately 50% pure. The most polar component isolated (fractions 22-25) was assigned as the second diastereomer (395 mg, 8%); mp: 127.5-129.3 * C; i H NMR (300 MHz, CDCI3) δ 7.56 (d, J = 8.6 Hz, 2H) , 6.87 (d, J = 8.6 Hz, 2H) , 5.25 (d, J = 9.5 Hz, IH) , 4.87 (m, IH) , 4.35 (dt, J = 9.2, 3.7 Hz, IH) , 4.15 (bs, 2H) , 3.81, (d, J = 6.2 Hz, 2H) , 3.78 (s, 3H) , 3.49 (dd, J = 16.5, 10.3 Hz, IH), 3.05 (t, J = 7.7 Hz, 2H) , 2.97 (dd, J = 16.5, 7.0 Hz, IH) , 2.73 (bt, J = 12.1 Hz, 2H) , 2.21 (m, IH) , 1.94 (m, 2H), 1.82 (m, 4H) , 1.45 (s, 9H) , 1.24 (m, 3H) , 0.92 (t, J = 7.3 Hz, 3H) . Part D. 3-(3- \4- ( (Butyloxycarbonylpiperidin-4-yl)methox- ylphenvllisoxazolin-5-yl( rhutanesu! fonyl 1amino!) - propionic Acid (More Polar Diastereomer) A solution of methyl 3- (3- [4-{ (butyloxycarbonylpi- peridin-4-yl)methoxyJphenyl] isoxazolin-5-yl{ [butanesul- fonyl]amino})propionate more polar diastereomer (200 mg, 0.344 mmol) in THF (1 mL) was saponified using 0.5M LiOH (1 mL, 0.5 mmol) over 4 hours as per Example 1, Part F. The crude carboxylic acid was crystallized from EtOAc/hexanes, affording 77 mg (39%) of the desired material; mp: 137.3-139.0 * C; X H NMR (300 MHz, CDCI3) δ 7.55 (d, J = 8.8 Hz, 2H) , 6.87 (d, J = 8.8 Hz, 2H) , 5.45 (d, J = 9.5 Hz, IH) , 4.92 (m, IH) , 4.37 (m, IH) , 4.15 (b, 2H) , 3.81, (d, J = 6.2 Hz, 2H) , 3.47 (dd, J = 16.5, 9.9 Hz, IH) , 3.08 (t, J = 8.1 Hz, 2H) , 3.01 (dd, J = 16.5, 7.0 Hz, IH) , 2.74 (bt, J = 12.1 Hz, 2H) , 2.26 (m, IH) , 2.01 (m, 2H) , 1.81 (m, 4H) , 1.45 (s, 9H, overlapped with m, IH) , 1.24 (m, 3H) , 0.91 (t, J = 7.3 Hz, 3H) . Part D' . 3-(3-T4-( (Butyloxvcarbonylpiperidin-4-vl) eth¬ oxyIphenvll isoxaznlin-5-yl { rhntanesπlfonyl!amino))- propionic Acid (Less Polar Diastereomer) A solution of the impure methyl 3- (3- [4-{ (butylox- ycarbonylpiperidin-4-yl)methoxy}phenyl] isoxazolin-5- yl{ [butanesulfonyl]amino})propionate less polar diastereomer (309 mg) in THF (5 mL) was saponified using 0.5M LiOH (2 mL, 1 mmol) over 6 hours as per Example 1, Part F. The crude carboxylic acid was purified using flash chromatography (CHCI3 - 5-15% MeOH/CHCl3 step gradient) followed by crystallization from EtOAc/hexanes, affording 169 mg of the desired material; mp: 155 * C (dec); i H NMR (400 MHz, DMSO-dβ, 80 'C) δ 7.56 (d, J = 8.8 Hz, 2H) , 6.98 (d, J = 8.8 Hz, 2H) , 4.80 (m, IH) , 3.96 (bd, J = 13.2 Hz, 2H) , 3.90 (d, J = 6.3 Hz, 2H) , 3.77 (bs, 3H) , 3.52 (t, J = 7.8 Hz, IH) , 3.38 (dd, J = 14.4, 10.0 Hz, IH) , 2.98 (t, J = 7.8 Hz, 2H) , 2.76 (dt, J = 12.2, 1.7 Hz, 2H) , 1.95 (m, 2H) , 1.75 (m, 4H) , 1 . 41 ( s , 9H) , 1 .38 (d, J = 7 . 6 Hz , IH) , 1 . 25 (m, 4H) , 0 . 88 (t , J = 7 . 3 Hz , 3H) . Part E. 3-(3-[4-f (Piperidin-4-yl)methpxyϊphenyllisoxa- zolin-5-ylf rbutanesulfonyl!amino!)propionic Acid, Trifluoroacetic Acid Salt (More Polar Diastereomer) 3- (3- [4-{ (Butyloxycarbonylpiperidin-4-yl)methox- y}phenyl] isoxazolin-5-yl{ [butanesulfonyl]amino})propion- ic acid more polar diastereomer(40 mg, 0.070 mmol) was Boc-deprotected using 33% TFA/DCM according to Example 1, Part G. Recrystallization from methanol then afforded 4 mg (10%) of the TFA salt; mp: 263.5 * C (dec) . Part E'. 3-(3-r4-f (Piperidin-4-yl ) ethoxyIphenyl1 i snxa- zolin-5-ylf fbutanesulfonyl!amino!)propionic Acid r Trifluoroacetic Acid Salt (Less Polar Diastereomer) 3- (3- [4-{ (Butyloxycarbonylpiperidin-4-yl)methox- yjphenyl]isoxazolin-5-yl{ [butanesulfonyl]amino})propion¬ ic acid less polar diastereomer(98 mg, 0.173 mmol) was Boc-deprotected using 33% TFA/DCM according to Example 1, Part G, giving 40 mg of the TFA salt. Recrystallization from methanol then afforded 28 mg (29%) of the pure amino acid; mp: 239.4-240.7 * C. Example 33 4-Carboxymethyl-3- \ 4- (2-piperidin-4-yl )ethoxyphenyl!- (5ft.S)-isoxazolin-5-vlacetic Acid. Trifluoroacetic Acid Sal This material was prepared analogously to Example 1, giving the desired material; mp: 141.4 'C (dec); i H NMR (400 MHz, CD3OD, 60 * C) 57.60 (d, J = 8.8 Hz, 2H) , 6.96 (d, J = 8.8 Hz, 2H) , 3.84 (d, J = 17.3 Hz, IH) , 3.66 (s, 3H) , 3.59 (d, J = 17.3 Hz, IH) , 3.38 (bd, J = 12.9 Hz, IH), 3.24 (t, J = 1.7 Hz, 2H) , 3.21 (dm, J = 20.3 Hz, IH) , 3.04 (d, J - 1.5 Hz, 2H) , 3.00 (dt, J = 12.9, 2.9 Hz, 2H) , 2.02 (bd, J = 14.4 Hz, 2H) , 1.95 (m, IH) , 1.81 (m, 2H), 1.48 (m, 2H) . Example 43 3 (ft..<?) -f5 (ft. S) -N- r3- (4-Amidinophenyl) isoxazolin-5- ylacetyllaminol-3-phenylpropanoic Acid Part A. 4-Cyanobenzaldoxime This material was prepared from 4-cyanobenzaldehyde according to Kawase and Kikugawa (J. Chem. Soc. Perkin Trans I 1979, 643) . Part B. Methyl 3- (3-Butenoyl) amino-3-phenylpropionate To a solution of vinylacetic acid (861 mg, 10.0 mmol) , methyl 3-amino-3-phenylpropionate hydrochloride (2.37 g, 11.0 mmol) and TEA (1,6 mL, 12 mmol) in DCM (20 mL) at -10 "C was added DEC (2.11 g, 11.0 mmol) . The resulting mixture was stirred at -10 * C for 15 hours. The mixture was then washed with water, 0.1 M HCI, sat. NaHCθ3, sat. NaCl and dried over anhydrous MgS04. Concentration in vacuo followed by pumping until constant weight was achieved gave 2.36 g (95%) of the desired amide as a golden oil of suitable purity for further reaction; iH NMR (300 MHz, CDCI3) 57.28 (m, 5H) , 6.78 (bd, J = 7.7 Hz, IH) , 5.95 (m, IH) , 5.43 (dt, J = 8.4, 5.9 Hz, IH) , 5.25 (m, 2H) , 3.61 (s, 3H) , 3.04 (d, J = 7.0 Hz, 2H) , 2.88 (dq, J = 15.0, 5.9 Hz, 2H) . Part C. Methyl 3 (ft. <?)-( (ft. <?)-N- T3- (4-Cyanophen- yl) isoxazolin-5-ylacety11amino1-3-phenylpropanoate This material was prepared from methyl 3- (3- Butenoyl)amino-3-phenylpropionate (816 mg, 3.30 mmol) and 4-cyanobenzaldoxime (438 mg, 3.00 mmol) according to Example 4, Part B. The crude product was then purified using flash chromatography (70% EtOAc/hexanes) , affording 731 mg (62%) of the desired isoxazolines as a 1:1 mixture of diastereomers; X H NMR (300 MHz, CDCI3) 5 7.74 (m, 8H), 7.29 (m, 10H) , 6.92 (bm, 2H) , 5.42 (m, 2H) , 5.16 (m, 2H) , 3.64 (s, 3H) , 3.60 (s, 3H) , 3.48 (m, 2H) , 3.26 (dd, J = 17.3, 7.7 Hz, IH) , 3.15 (dd, J = 16.8, 8.1 Hz, IH) , 2.85 (m, 2H) , 2.69 (m, 2H) . Part D. Methyl 3 (R, S)-f5 IR, S)-N-T3-(4-Amidinophen- yl)ispχazplin-5-ylacetyl1amino1-3-phenylpropanpat.e Into a solution of methyl 3 (ft, S)-{5 (ft,S)-N- [3-(4- cyanophenyl) isoxazolin-5-ylacetyl]amino}-3-phenylpro- panoate (587 mg, 1.50 mmol) in 10% DCM/methanol (55 mL) was bubbled dry HCI gas for 2 hours. The mixture was stirred for 18 hours, then concentrated in vacuo . The crude imidate was dissolved in methanol (20 mL) and ammonium carbonate added. The resulting mixture was stirred for 18 hours, then filtered. The filtrate was concentrated in vacuo and the residue purified using flash chromatography (CHCI3 - 20% methanol/CHCl3) . Concentration of the appropriate fractions in vacuo followed by placing the residue under vacuum until constant weight was achieved afforded 193 mg (32%) of the desired amidines; Mass Spectrum (NH3-DCI, e/z, relative abundance) 409 (M + H) + , 100%. Part E . 3 IR, S) - f 5 (R, >?) -N- f3- ( 4-Amidinophenyl ) i fioxazolin- 5-ylacetyll aminol-3-phenylpropanoio Arid. Trifluoroace¬ tic Acid Salt Methyl 3 (ft, S)-{5 (ft,S)-N- [3- (4-amidinophen-yl) isoxa- zolin-5-ylacetyl]amino}-3-phenylpropanoate (45 mg, 0.113 mmol) was saponified using 0.5 Λf LiOH (0.6 mL, 0.3 mmol) according to Example 1, Part F, affording 28 mg (49%) ; Mass Spectrum (NH3-DCI, e/z, relative abundance) 412 (M + H) + , 100%. Example 120a Methyl 3 (ft)-(5 (ft..9) -At- T - (4-amid nophenyl) i soxazo n-5- ylacetyl1amino1-3-phenethylpropanoate Part A. (E)-Methvl-5-phenyl-2-pentenoate A solution of hydrocinnamaldehyde (13.42 g, 0.1 mol) and methyl (triphenylphosphoranylidene)acetate (33.44 g, 0.1 mol) in THF was stirred at reflux for 20 hours. The reaction mixture was concentrated under vacuum and the residue was purified by flash chromatography using hexane:EtOAc: : 9:1. The desired product was obtained as a clear, pale yellow oil (8.0 g, 0.042 mol, 42%); i H NMR (300 MHz, CDCI 3 ) 5 7.3-7.2 (m, 2H) , 7.2-7.1 (m, 3H) , 7.1-6.9 (m, IH) , 5.85 (d, IH, J = 5.8 Hz), 3.75 (s, 3H) , 2.8 (t, 2H, J = 7.7 Hz), 2.55 (q, 2H, J = 7.4 Hz); MS (NH3-DCI) 191 (M+H) + . Part B. Methyl 3- (ft)- ._V- (1- (ft) -1-phenylethyl ) amino!-5- phenylpentanoate A mixture of (E) -methyl-5-phenyl-2-pentenoate (5.70 g, 0.03 mol) and ft-methylbenzylamine (14.54 g, 0.12 mol) was heated at 110°C over 94 hours. The cooled reaction mixture was purified by flash chromatography using hexane:EtOAc: :8:2 to afford 1.18 g (0.0038 mol, 12%) of the desired product as a clear liquid; 1 R NMR (300 MHz, CDC1 3 ) δ 7.4-7.0 (m, 11H) , 3.9 (q, • IH, J = 6.5 Hz), 3.65 (s, 3H) , 2.9-2.65 ( , 2H) , 2.6-2.35 (m, 3H) , 1.75-1.6 (m, 2H) , 1.35 (d, 3H, J = 6.2 Hz); MS (NH3-DCI) 312 (M+H) + . Part C. Methyl 3- (ft)-amino-5-phenylpentanoate » acetic A mixture of methyl 3- (ft)- [N- (1- (ft) -1- phenylethyl)amino]-5-phenylpentanoate (0.72 g, 2.3 mmol), 20% Pd(OH)2/C (0.38 g) , cyclohexene (8.2 mL) , glacial HOAc (0.13 mL, 2.3 mmol), and MeOH (15 mL) was heated at reflux under N 2 for 20 hours. After cooling, the catalyst was removed by filtration through a Celite plug, rinsed with MeOH, and the solution concentrated under vacuum. The residue was triturated with hexane to afford 0.46 g (96%) of a white solid, mp = 73-75°C ; i H NMR (300 MHz, DMSO) δ 8.3 (bs, 2H) , 7.35-7.15 (m, 5H), 3.65 (s, 3H) , 3.45-3.35 (m, IH) , 2.8-2.6 (m, 4H) , 2.0-1.7 (m, 2H) ; [CC] D 25 -12.50° (c=0.0032, MeOH) . Part D. Methyl 3 (ft)-f5 (ft. S) -N- [3- ( 4- cyanophenyl) isoxazolin-5-ylacetyllaminoIheptanoate To a suspension of 3- (4-cyanophenyl) isoxazolin-5- ylacetic acid (460 mg, 2.0 mmol) in EtOAc (15 ml) was added methyl 3- (ft)-amino-5-phenylpentanoate acetic acid salt (410 mg, 2.0 mmol), TBTU (640 mg, 2.0 mmol), and Et3N (0.56 mL, 400 mg, 4.0 mmol) . After stirring at room temp for 16 hours, the reaction mixture was concentrated under vacuum then purified by flash chromatography using EtOAc to afford 690 mg (83%) of a colorless oil. i H NMR (300 MHz, DMSO) δ 8.05 (brs, IH) , 7.95-7.9 (m, 2H) , 7.85-7.8 (m, 2H) , 7.3-7.25 ( , 2H) , 7.2-7.1 ( , 2H), 5.15-5.0 (m, IH) , 4.15-4.0 (m, IH) , 3.6 (d, 3H, J = 9.9 Hz), 3.3 (d, 2H, J = 6.9 Hz), 3.25-3.15 (m, IH), 2.75-2.35 (m, 6H) , 1.8-1.6 (m, 2H) ; MS (NH 3 - DCI) 420 (M+H) + . Part E Methyl 3 (ft)-f5 (ft. S) -N- L3- (4- a idinophenyl) soxazol in-5-yl cetyl 1aminol-3- phenethylpropanoate This material was prepared from methyl 3(ft)- {5 (ft, S) -N- [3-(4-cyanophenyl) isoxazolin-5- ylacetyl]amino}-3-phenethylpropanoate (670 mg, 1.6 mmol) according to Example 43, Part D. The crude product was triturated with cold ether to afford 272 mg (39%) of a white solid of the title compound as a 1:1 mixture of diastereomers, mp = 76-78°C; X H NMR (300 MHz, DMSO) δ 8.1-8.0 (m, IH) , 8.0-7.8 (m, 4H) , 7.95-7.85 (m, 5H) , 7.35-7.2 (m, 5H) , 5.1-5.0 (m, IH) , 4.1-4.0 (m, IH) , 3.6 (s, 3H), 3.3-3.15 (m, 2H) , 2.7-2.4 (m, 6H) , 1.8-1.7 (m, 2H) , 1.1-1.0 (m, 2H) ; Mass Spectrum (NH3-ESI, ) 437 (M + H) + . Example 120b Methvl 3 (S) - f 5 (ft. S) -N- r3- (4-amidinophenvl) isoxazolin-5- ylacetyl1 mino1-3-phenethylpropanoate Part A. Methyl 3- (S) - fN- (1- (ft)-1-phenylethyl) amino!-5- phenylpent.anoate A mixture of (E) -methyl-5-phenyl-2-pentenoate (5.70 g, 0.03 mol) and ft-methylbenzylamine (14.54 g, 0.12 mol) was heated at 110°C over 94 hours. The cooled reaction mixture was purified by flash chromatography using hexane:EtOAc: :8:2 to afford 1.20 g (0.0039 mol, 13%) of the desired product as a clear liquid; i H NMR (300 MHz, CDCI3) δ 7.35-7.0 (m, 11H) , 3.9 (q, IH, J = 6.6 Hz), 3.65 (s, 3H) , 2.95-2.8 (m, IH) , 2.75-2.5 (m, 2H) , 2.45- 2.35 (m, 2H), 1.9-1.65 (m, 2H) , 1.3 (d, 3H, J = 6.6 Hz); MS (NH3-DCI) 312 (M+H) + . Part B. Methyl 3- (£)-amino-5-phenylpentanoate » acetic acid salt Methyl 3-(S)- [N-benzyl-N- (1- (ft)-1- phenylethyl)amino]heptanoate (0.93 g, 2.9 mmol), 20% Pd(OH) 2 /C (0.47 g) , cyclohexene (10.1 mL) , glacial HOAc (0.17 mL, 2.9 mmol), and MeOH (20 mL) were heated at reflux under Ν2 for 48 hours. After cooling, the catalyst was removed by filtration through a Celite plug, rinsed with MeOH, and the solution concentrated under vacuum. The residue was triturated with hexane to afford 0.65 g (80%) of a white solid, mp = 86-88°C; X H NMR (300 MHz, CDCI3) δ 7.35-7.15 (m, 5H) , 5.3 (brs, 2H) , 3.65 (s, 3H), 3.35-3.2 (m, IH) , 2.8-2.55 (m, 3H) , 2.5- 2.4 (m, IH) , 2.0 (s, 3H) , 1.8 (q, 2H, J = 1.4 Hz); [α] D 25 +9.55° (c=0.220, MeOH) . Part C. Methyl 3 (.<?-(5 (ft.£) -N- 3-l4- cyanpphenyl)ispχazplin-5-ylacet.yl1a inpϊheptanoate To a suspension of 3- (4-cyanophenyl) isoxazolin-5- ylacetic acid (700 mg, 2.6 mmol) in EtOAc (15 ml) was added methyl 3-(S)-amino-5-phenylpentanoate acetic acid salt (600 mg, 2.6 mmol), TBTU (830 mg, 2.6 mmol), and Et3N (1.09 mL, 790 mg, 7.8 mmol) . After stirring at room temp 16 hours, the reaction mixture was concentrated under vacuum then purified by flash chromatography using EtOAc to afford 420 mg (38%) of a colorless oil. i H NMR (300 MHz, CDCI3) δ 8.05-8.0 (m, IH), 7.95-7.9 (m, 2H) , 7.85-7.8 (m, 2H) , 7.3-7.2 (m, 2H), 7.2-7.1 (m, 3H) , 5.15-5.0 (m, IH) , 4.15-4.0 (m. 1H) , 3 . 6-3 . 55 (m, 3H) , 3 .3-3 . 1 (m, IH) , 2 . 7-2 . 4 (m, 6H) , 1 . 8-1 . 6 (m, 2H) ; MS (NH3-DCI ) 420 (M+H) + . Part D. Methyl 3 (S)-f5 (ft, S) -N- T3- (4- amidinophenyl) isoxazolin-5-ylacetyllamino1-3- phenethylpropanpate This material was prepared from methyl 3(5)- {5 (ft, S) -N- [3- (4-cyanophenyl) isoxazolin-5- ylacetyl]amino}-3-phenethylpropanoate (360 mg, 0.86 mmol) according to Example 43, Part D. The crude product was triturated with cold ether to afford 230 mg (62%) of an amorphous solid of the title compound as a 1:1 mixture of diastereomers, mp = 84-86°C; i H ΝMR (300 MHz, DMSO) δ 8.1-8.0 (m, IH) , 8.0-7.8 (m, 4H) , 7.75-7.7 ( , IH), 7.3-7.1 (m, 6H) , 5.1-5.0 (m, IH) , 4.15-4.0 (m, IH), 3.65 (s, 3H) , 3.3-3.1 (m, IH) , 2.7-2.6 (m, 3H) , 2.5-2.4 (m, 3H) , 1.8-1.65 (m, 2H) , 1.1-1.0 (m, 2H) ; Mass Spectrum (ΝH3-ESI) 437 (M + H)+. Example 189 5 (ft. S) - (2-Piperidin-4-yl )ethyl-8- (2-carhoxyethyl)-1-oxa- 2.8-diazaspiro .41non-2-ene-7. -dione Part A. 3-(W-t-BυtylPχycarbpnylpiperidin-4-yl)prppanal To a suspension of PCC (11.52 g, 53.44 mmol) and sodium acetate (4.38 g, 53.4 mmol) in DCM (60 mL) was added a solution of 3- (N-t-butyloxycarbonylpiperidin-4- yl)propanol (10.00 g, 41.09 mmol) in DCM (20 mL) . After 4 hours at room temperature, the mixture was diluted with ether and passed though a short column of fluorisil® using ether as an eluent. The eluate was concentrated in vacuo and placed under vacuum until constant weight was achieved, affording 8.32 g (84%) of the desired aldehyde as a colorless oil; H NMR (300 MHz, CDCI3) 59.76 (t, J - 1.5 Hz, IH) , 4.05 (bs, 2H) , 2.64 (bt, J = 11.7 Hz, 2H) , 2.45 (dt, J = 7.3, 1.5 Hz, 2H) , 1.60 (m, 3H) , 1.43 (s, 9H, overlapped with m, 2H) , 1.08 (dq, J = 12.1, 4.0 Hz, 2H) . Part B. (E. Z)-3- (N- -Butvloxycarbonylpiperidin-4-yl)pro- panal Qxi e To a solution of 3- (N-t-butyloxycarbonylpiperidin- 4-yl)propanal (3.905 g, 16.18 mmol) in EtOH : pyr = 1 : 1 (20 mL) was added hydroxylamine hydrochloride (1.701 g, 24.48 mmol) and the resulting solution stirred at room temperature for 20 hours. Concentration in vacuo, resulted in an oil, which was dissolved in EtOAc and washed with 0.1 Λf HCI (3x) , water, sat. CUSO 4 (2x) , water and brine. The solution was dried over MgS0 4 , concentrated in vacuo and placed under vacuum until constant weight was achieved, affording 4.071 g (98%) of a 1 : 1 mixture of the (E, Z) -oxime as a colorless oil; i H ΝMR (300 MHz, CDCI3) 57.42 (t, J = 6.2 Hz, 0.5H), 6.70 (t, J = 5.5 Hz, 0.5H), 4.06 (bs, 2H) , 2.67 (bt, J = 12.8 Hz, 2H), 2.41 (m, IH) , 2.23 (m, IH) , 1.66 (b, 2H) , 1.45 (s, 9H, overlapped with m, 4H) , 1.08 (m, 2H) . Part C. Methyl (5ft. ?)-3-( F2- (AT-t-Butyloxycarbonylpiperi- din-4-yl)ethyl!-5-carboxymethylisoxazolin-5-yllacetate To a solution of (£., Z) -3- (N-t-butyloxycarbonylpi- peridin-4-yl)propanal oxime (503 mg, 1.96 mmol) and dimethyl itaconate (620 mg, 3.92 mmol) in DCM (3 mL) was added a 5% solution of sodium hypochlorite (common household bleach, 3 mL, 2 mmol) . The resulting mixture was stirred overnight (19 hours) at room temperature. The layers were separated and the aqueous washed with DCM (2x) . The combined DCM fraction was dried over MgS0 4 and concentrated in vacuo . Purification using flash chromatography (hexanes - 10% EtOAc/hexanes - 50% EtOAc/hexanes) followed by concentration and pumping to constant weight afforded the desired isoxazoline (510 mg, 63%) as a colorless oil; 2 H NMR (300 MHz, CDCI3) 5 4.06 (bd, J = 13.6 Hz, 2H) , 3.78 (s, 3H) , 3.67 (s, 3H) , 3.57 (d, J = 17.6 Hz, IH) , 3.15 (d, J = 16.5 Hz), 3.06 (d, J = 17.6 Hz, IH) , 2.86 (d, J = 16.5 Hz, IH) , 2.65 (bt, J = 12.1 Hz, 2H) , 2.36 (m, 2H) , 1.65 (m, 2H, overlapped with H 2 0, 2H) , 1.43 (s, 9H) , 1.07 (m, 2H) . Part D. (5fl,g)-3-f f2-(N-£-Butylpχycarbpnylpiperidin-4- yl)ethyl1-5-carbPxyispχazplin-5-yl}acetic Acid To a solution of methyl (5ft,S)-3-{ [2- (N-t-butyloxy- carbonylpiperidin-4-yl) ethyl]-5-carboxymethylisoxazol- in-5-yl}acetate (380 mg, 0.921 mmol) was saponified using 0.5Λf LiOH (5 mL, 2.5 mmol) in THF (5 mL) . The reaction was stirred at ambient temperature for 5 hours, according to Example 1, Part F to give 240 mg (68%) of the diacid; mp: 154.4-154.9 * C; i H ΝMR (300 MHz, MeOH- d ) 54.04 (bd, J = 13.2 Hz, 2H) , 3.52 (d, J = 17.8 Hz, IH) , 3.18 (d, J = 17.8 Hz, IH) , 2.97 (AB quartet, Δ = 32.6, J = 16.8 Hz, 2H) , 2.72 (b, 2H) , 2.39 (m, 2H) , 1.71 (bd, J = 13.2 Hz, 2H) , 1.51 (m, 3H) , 1.43 (s, 9H) , 1.05 (m, 2H) . Part E. 5 (ft S)-2- (N-t-Butyloxycarbonylpiperidin-4- yl)ethyl-8- T (2- (1.1-dimethylethoxycarbonyl) thyl!-1-oxa- 2.8-dia aspiror4.41non- -ene-7. -dione To a solution of (5ft,S)-3-{ [2- (N-t-butyloxycarbon- ylpiperidin-4-yl) ethyl]-5-carboxyisoxazolin-5-yl}acetic acid (700 mg, 1.82 mmol) in THF (5 mL) was added DCC (378 mg, 1.83 mmol), and the resulting suspension was stirred for 30 min at room temperature. To this mixture was added a suspension of ϊ-alanine t-butyl ester hydrochloride (372 mg, 2.05 mmol) and TEA (300 μL, 2.15 mmol) in THF (5 mL) . The mixture was stirred overnight (18 hours) at room temperature. Following dilution with EtOAc, the mixture was filtered and the filtrate washed with O.lΛf HCl, sat. NaHCθ3 and sat. NaCl. It was dried over anhydrous MgS04, concentrated and placed under vacuum until constant weight was reached, giving 430 mg (46%) of the crude amide. A portion of this material (420 mg, 0.821 mmol) was dissolved in THF (4 mL) . To this solution was added HOSuc (100 mg, 0.869 mmol) followed by DCC (180 mg, 0.872 mmol) . The resulting suspension was stirred at room temperature for 18 hours. Following dilution with ether, the mixture was cooled to 0 * C and filtered. The filtrate was dried over anhydrous MgS04, concentrated and placed under vacuum until constant weight was reached, giving 430 mg (86%) of the crude active ester. A portion of this material (402 mg, 0.660 mmol) was dissolved in DMF (5 mL) at 0 * C. To this solution was added NaH (16 mg, 0.66 mmol) . After 3 hours at 0 "C, the reaction was quenched with HOAc. After dilution with EtOAc, the mixture was washed with water (4x) , sat. NaHC03, water, O.lΛf HCl and sat. NaCl. It was dried over anhydrous MgS04, concentrated and placed under vacuum until constant weight was reached, giving 230 mg (70%) of the crude imide. The crude material was purified using flash chromatography (CHCI3 - 5% MeOH/CHCl 3 ), affording 149 mg (46%) of a colorless oil after concentration of the appropriate fractions and -pumping to constant weight; i H NMR (300 MHz, CDCI3) 54.09 (b, 2H) , 3.82 (t, J = 7.3 Hz, 2H) , 3.54 (d, J = 17.2 Hz, IH) , 3.12 (d, J = 18.7 Hz, IH) , 2.98 (d, J = 17.2 Hz, IH) , 2.83 (d, J = 18.7 Hz, IH) , 2.69 (m, 2H), 2.57 (t, J = 7.3 Hz, 2H) , 2.42 (m, 2H) , 1.68 (m, 2H) , 1.57 (m, 2H) , 1.45 (s, 9H, coincident with m, IH) , 1.11 (m, 2H) . Part F . 5 (ft. S) - (2-Pi peridin-4-yl ) ethyl -fi- 17- carhoxvethvl ) -l -oxa-2. 8-diaza spi ro F4 . 41 non-2-ene-7. 9- To a solution of 5 (R, S) -2- ( N-t-butyloxycarbon- ylpiperidin-4-yl)ethyl-8- [ (2- (1, 1-dimethylethoxycarbon- yl)ethyl]-l-oxa-2, 8-diazaspiro[4.4]non-2-ene-7, 9-dione (75 mg, 0.152 mmol) in DCM (1 mL) was added TFA (0.5 mL, 8 mmol) . The reaction was stirred at room temperature for 2 hours, then was concentrated in vacuo . Excess TFA was chased by rotary evaporation with toluene (2x) . Crystallization from MeOH/ether gave 10 mg (15%) of the desired amino acid after pumping to constant weight; mp: 178.0-179.1 'C; H ΝMR (400 MHz, DMSO-d 6 , 60 * C) 512.15 (bs, IH) , 8.26 (bs, 2H) , 3.64 (m, 2H) , 3.39 (d, J = 17.8 Hz, IH) , 3.26 (m, 3H) , 2.98 (AB quartet, Δ = 71.3 Hz, J = 18.3 Hz, 2H), 2.85 (m, 2H) , 2.50 (m, IH, coincident with DMSO-d 5 ) , 2.37 (t, J = 7.6 Hz, 2H) , 1.84 (bd, J = 11.7 Hz, 2H), 1.58 (m, IH) , 1.52 (t, J - 7.6 Hz, 2H) , 1.29 (m, 2H) . Example 190 (ft. S) - (2-Piperidin-4-yl)ethyl-8- (3-carboxvpropyl)-1- oxa-2.8-diazaspiroT4.41non-2-ene-7. -dione This material was prepared using the procedures outlined in Example 189, giving the title compound; mp: 133.4-135.1 * C; i H ΝMR (400 MHz, CD 3 OD, 55 * C) 53.59 (t, J = 6.8 Hz, 2H) , 3.50 (d, J = 17.7 Hz, IH) , 3.38 (bd, J = 12.9 Hz, 2H) , 3.18 (d, J = 17.7 Hz, IH) , 2.98 (m, 4H) , 2.85 (m, 2H) , 2.50 (m, IH, coincident with DMSO-ds) , 2.45 (m, 2H), 2.31 (t, J = 7.1 Hz, 2H) , 2.00 (m, 2H) , 1.98 (pentuplet, J = 7.1 Hz, 2H) , 1.40 (m, 2H) . Example 275 N-3--r -(4-ami inophenvl) isoxazol in-5 (ft. <7) -ylacetyl! -L- 2.3-diaminppropinoin acid TFA sal Part A. 3- (4-ovanophenyl ) i soxa zolin-5 (ft . <?) -yl aoet ic To a solution of 4-cyanobenzaldoxime (see Ex 43, Part A) (312 g, 2.13 mol) in tetrahydrofuran (3000 ml) at room temperature was added vinyl acetic acid (552g, 6.41 mol) . The yellow solution was cooled in an ice bath and sodium hypochlorite solution (5200 ml)was added in a dropwise fashion over 2h. After stirring overnight at room temperature the reaction was quenched with a 5% citric acid solution and diluted with 200ml ether. The layers were separated and the aqueous acidified to pH 4 using citric acid. The acid layer was washed twice with 200 ml ether, the ether layers combined and extracted with saturated sodium bicarbonate solution. After acidifying the basic layer with citric acid, the product was extracted into 400 ml ether. The organic phase was washed three times with 150 ml water, once with brine, dried (MgS0 4 ) and concentrated to give 220g of 3-(4- cyanophenyl) isoxazolin-5-ylacetic acid as a white solid. Recrystallization from 25% water/ethanol yielded 165g of analytically pure material. Anal. Calcd for C 1 2H 1 0N 2 O3: C 62.61; H,4.38; N, 12.17. Found: C, 62.37; H 4.47; N, 11.71. H NMR(300MHz, CDCI3) : δ 7.77-7.76 (d, 2H, J=1.8Hz); 7.72-7.71 (d, 2H, J=1.8Hz); 5.22-5.14 (m, IH) ; 3.63-3.54 (dd, IH, J=10.6Hz, 16.8Hz); 3.19-3.11 (dd, IH, J=7.3Hz, 16.8Hz); 3.00-2.93 (dd, IH, J=6.2Hz, 16.5Hz); 2.79-2.72 (dd, IH, J=7.3Hz, 16.5Hz) . IR(KBr pellet) : 3202, 2244, 1736, 1610, 1432, 1416, 1194, 1152, 928, 840, 562 cm" 1 . Part B. Methyl N2.-Chz-r.-2.3-diaminopropionate HCI salt. N 2 -Cbz-X-2,3-diaminopropionic acid (10 mmol, 2.39 g) was dissolved in 20 mL methanol and 20 mL 4 N HCI in dioxane and the solution was stirred for 4 hours and then concentrated to give a solid. The solid was washed with ether several times to give 2.50 g (87%) product. NMR (DMSO-d δ ) : δ 8.38 (b, 3H) ; 7.96 (d, IH) ; 7.38 (m, 5H) ; 5.05 (s, 2H) ; 4.44 (m, IH) ; 3.66 (s, 3H) ; 3.14 (m, 2H) . Part C. Methyl N^-Cbz-N-^- Ϊ3- (4-cyanophenyl ) isoxazolin- 5 (ft. S) -ylacetyl -L-2 r 3-diaminopropionate. To a solution of 3- (4-cyanophenyl) isoxazolin-5 (ft, S)-ylacetic acid. (19 mmol, 4.37 g) , methyl N 2 -Cbz-L- 2,3-diaminopropionate HCI salt (20 mmol, 5.76 g) and triethylamine (60 mmol, 8.36 mL) was added TBTU (20 mmol, 6.42 g) and the solution was stirred for 2 hours. Ethyl acetate was added and the solution was washed with dilute citric acid, brine, NaHCθ3 and brine, dried (MgSθ 4 ), and concentrated. Crystallization from ethyl acetate/ether gave 6.85 g (78%) product. NMR (DMSO-dβ) : δ 8.16 (t, IH) ; 7.92 (d, 2H) ; 7.82 (d, 2H) ; 7.68 (d, IH) ; 7.36 (m, 5H) ; 5.04 (m, 3H) ; 4.20 (m, IH) ; 3.64 (s, 3H) ; 3.50 (m, 2H) ; 3.26 (m, 2H);2.50 (m, 2H) . Part D. Methyl N^- T3- (4-amidinophenyl) isoxazolin-5 (ft. S)-vlacetvll- -2.3-diaminopropionate HCI salt. HCI gas was bubbled into a solution of methyl N 2 - Cbz-N 3 - [3-(4-cyanophenyl) isoxazolin-5 (ft, S)-ylacetyl] -L- 2, 3-diaminopropionate (2.1 mmol, 1.0 g) for 1 hour and the solution was stirred overnight and concentrated. The residue was dissolved in 30 mL 2 M ammonia in methanol and the solution was stirred overnight, and concentrated to give 1.2 g crude product. E. N 3 -- r3-(4-amidinophenyl ) i soxπzolin- (ft. .<?) -ylaretyl 1- L-2 f 3-diaminopropionic acid TFA salt. Methyl N 3 - [3- (4-amidinophenyl) isoxazolin-5 (ft, 5) - ylacetyl]-L-2,3-diaminopropionate HCI salt (200 mg) was saponified with 1 mL methanol and 1 mL 1 N NaOH for 1 hour and acidified with acetic acid. Purification on reversed phase HPLC gave 40 mg product. ESI (M+H) + : Calcd 334.2; Found 334.2. Example 276 N^-Cbz-N3-r3-(4-amidinophenyl) isoxazolin-5 (ft. S) - vlacetvll- -2.3-diaminopropionic acid TFA salt Part A. Methyl N^-Cbz-N-- 3- (4- amidinophenvl) isoxazolin-5 (ft. .9)-vlacetyl1-L-2.3- diaminopropionate TFA salt. To a solution of the compound of Ex. 275, part E (1.0 mmol, 385 mg) and sodium bicarbonate (5.0 mmol, 400 mg) in 2 mL water, 2 mL acetonitrile and 1 mL DMF was added benzyl chloroformate (1 mmol, 143 μL) and the mixture was stirred for 2 hours at room temperature. The solution was filtered, acidified with TFA and purified on reversed phase HPLC to give 150 mg (25%) product. NMR (DMSO-dβ) : δ 9.40 (s, 2H) ; 9.20 (s, 2H) ; 8.18 (t, IH) ; 7.86 (m, 4H) ; 7.68 (d, IH) ; 7.35 (m, 5H) ; 5.02 (m, 3H) ; 4.20 (m, IH) ; 3.64 (s, 3H) ; 3.52 (m, 2H) ; 3.26 (m, 2H) ; 2.50 (m, 2H) . Part B. N2.-c.bz-N 3 — T3- (4-amidinophenvl) isoxazolin-5 (ft, .9 -vlacetyl!-L-2.3-diaminopropionic acid TFA salt . Methyl N 2 -Cbz-N 3 - [3- (4-amidinophenyl) isoxazolin- 5 (ft, S)-ylacetyl]-L-2,3-diaminoproρionate TFA salt ( 0.12 mmol, 70 mg) was dissolved in 2 mL methanol and 1 mL 1 N NaOH and after 1 hour, the solution was acidified with acetic acid. Purification on reversed phase HPLC gave 50 mg (74%) product. ESI (M+H) + : Calcd 468.2; Found 468.2. Example 278 N2—n-butyloxycarbony1-N 3 --T3- (4-amidinophenyl) isoxazolin- 5(fl, g)-ylacetyl!-L-2,3-diaminoprppipnic acid TFA salt Part A. Methyl N2-n-butyloxycarbonvl-N3- L3- (4- amidinophenyl) isoxazolin-5 (ft r S)-ylacetyl 1-L-2, 3- diaminoprppipnat.e TFA salt. To a solution of the compound of Ex. 275, part E (1.0 mmol, 385 mg) and sodium bicarbonate (2.5 mmol, 200 mg) in 2 mL water, 2 mL acetonitrile and 1 mL DMF cooled in an ice bath was added n-butyl chloroformate (1 mmol, 127 μL) . After stirring for 1 hour, the solution was acidified with acetic acid and purified on reversed phase HPLC to give 150 mg (27%) product. NMR (DMSO-dδ) : δ 9.40 (s, 2H) ; 9.20 (s, 2H) ; 8.16 (t, IH) ; 7.86 (m, 4H) ; 7.47 (d, IH) ; 5.02 (m, IH) ; 4.16 (m, IH) ; 3.94 (t, 2H) ; 3.62 (s, 3H) ; 3.50 (m, 2H) ; 3.26 (m, 2H) ; 2.50 (m, 2H) ; 1.52 (m, 2H) ; 1.32 (m, 2H) ; 0.88 (t, 3H) . ESI (M+H) + : Calcd 448.3; Found 448.3. Part B. N2-n-butyloxycarbonyl-N3- T3- (4- amidinophenyl) isoxazolin-5 (ft, S)-ylacetyl!- (S) -2.3- diaminopropionic acid TFA salt. Methyl N2-n-butyloxycarbonyl-N3- [3- (4- amidinophenyl) isoxazolin-5 (ft, S)-ylacetyl]- (S) -2,3- diaminopropionate TFA salt (0.107 mmol, 60 mg) was dissolved in 2 mL methanol and 2 mL 1 N NaOH and after 1 hour, the solution was acidified with acetic acid. Purification on reversed phase HPLC gave 53 mg (89%) product. ESI (M+H) + : Calcd 434.3; Found 434.3. Example 314 A Methyl N^-n-butyloxycarbonyl-N 3 — 3- (4- amidinophenyl) isoxazol in-5 (S) -ylacetyl 1-(S)-2.3- diaminpprppjpnat.e TFA salt. Part A: Methvl N^-Cbz-N- 3 --Boc-L-?. -diaminoprooionate. To a solution of methyl N 2 -Cbz-(S)-2,3- diaminopropionate HCI salt (16.3 mmol, 4.7 g) and di- tert-butyl dicarbonate (16.3 mmol, 3.56 g) in 30 mL chloroform cooled in an ice bath was added triethylamine (34 mmol, 4.7 mL) and the solution was stirred in the ice bath for 1 hour and at room temperature for 3 hours and concentrated. The residue was taken up in ethyl acetate and the solution was washed with dilute citric acid, brine, NaHC03 and brine, dried (MgS0 4 ) , and concentrated. Crystallization from ether/petroleum ether gave 5.2 g (92%) product. NMR (DMSO-d δ ) : δ 7.60 (d, IH) ; 7.35 (m, 5H) ; 6.88 (t, IH) ; 5.02 (s, 2H) ; 4.14 (m, IH) ; 3.60 (s, 3H) ; 3.28 (m, 2H) ; 1.37 (s, 9H) . Part B: Methyl N 3 --Boc- (S) -7.3-disminopropionat HCQ 2 H sal . A mixture of methyl N 2 -Cbz-N 3 -Boc- (S) -2,3- diaminopropionate. (14 mmo, 5.0 g) , formic acid (42 mmol, 1.6 L) and 10% Pd/C (500 mg) in 40 mL methanol was stirred at room temperature for 1 hour and filtered through a celite. The filtrate was concentrated and the residue was triturated with ether-petroleum ether to give 3.7 g (100%) solid product. NMR (DMSO-dβ) : δ8.20(s, IH) ; 6.90 (t, IH) ; 5.36 (b, 3H) ; 3.61 9s, 3H) ; 3.51 (t, IH) ; 3.18 (t, 2H) ; 1.38 (s, 9H) . Part C: Methyl N^-n-butvloxycarbonvl-N^-Boc- (S)-2.3- diaminpprppipnat . To a mixture of methyl N3-B0C- (S)-2,3- diaminopropionate HCO 2 H salt (14 mmol, 3.7 g) and NaHC03 (40 mmol, 3.4 g) in 10 mL water and 10 mL THF cooled in an ice bath was added slowly butyl chloroformate (16 mmol, 2 mL) over 15 min. After stirring for 1 hour, ethyl acetate was added and the solution was washed with dilute citric acid, brine, NaHCθ3 and brine, dried (MgSθ 4 ) , and concentrated to give 4.4 g (100%) oily product. NMR (DMSO-dδ) : δ 7.37 (d, IH) ; 6.84 (t, IH) ; 4.10 (m, IH) ; 3.96 (t, 2H) ; 3.60 (s, 3H) ; 3.26 (m, 2H) ; 1.52 (m, 2H) ; 1.38 (s, 9H) ; 1.36 (m, 2H) ; 0.88 (t, 3H) . Part D: Methyl N^-hutyloxycarbonyl- (S)- . - diaminopropionate TFA salt . Methyl N 2 -n-butyloxycarbonyl-N 3 -Boc- (S)-2,3- diaminopropionate (13.9 mmol, 4.4 g) was dissolved in 25 mL methylene chloride and 35 mL TFA and after 1 hour, the solution was concentrated to give an oily product. Yield 4.8 g (100%) . NMR (DMSO-dβ) : 5 8.02 (b, 3H) ; 7.68 (d, 2H) ; 4.38 (m, IH) ; 3.99 (t, 2H) ; 3.68 (s, 3H) ; 3.22 (m, IH) ; 3.06 (m, IH) ; 1.55 (m, 2H) ; 1.34 (m, 2H) ; 0.89 (t, 3H) . Part E: Methyl-N^-n-butyloxycarbonyl-N 3 -- \ 3- (4- cyanophenyl) isoxazolin-5 (S)-ylacetyl!- (S)-2 r 3- diaminoprppipnate To a solution of 3- (4-cyanophenyl) isoxazolin-5 (S) - ylacetic acid (5.2 mmol, 1.2 g) [Chiral starting material was prepared from the racemic compound of Ex. 275, Part A by resolution on a 50 X 2 cm Chiralpak AD column using 0.1% TFA/EtOH at 10° C to give isomer A (faster eluting) and isomer B (slower eluting) . Alternately, the isomers were resolved by crystallization of the chinconidine salt of the 5-S isomer of the isoxazolines from acetone, leaving the 5 (R) isomer in the mother liquor. The absolute stereochemistry of the crystalline salt was determined by X-ray crystallography to be the 5(S) isoxazoline. ] and methyl N 2 -butyloxycarbonyl- (S)-2, 3-diaminopropionate TFA salt (6 mmol, 1.53 g) in 20 ml DMF cooled in an ice bath was added diisopropylethylamine (20 mmol, 3.5 mL) followed by BOP (5.5 mmol, 2.43 g) . After stirring at room temperature for 3 hours, ethyl acetate was added and the solution was washed with 0.5 N HCI, brine, NaHC03 and brine, dried (MgS0 4 ) , and concentrated to give 1.9 g (87%) product. NMR (DMSO-dβ) : δ 8.12 (t, IH) ; 7.94 (d, 2H) ; 7.83 (d, 2H) ; 7.46 (d, IH) ; 5.04 (m, IH) ; 4.16 (m, IH) ; 3.96 (t, 2H) ; 3.64 (s, 3H) ; 3.58 (dd, IH) ; 3.40 (m, 2H) ; 3.20 (dd, IH) ; 2.56 (dd, IH) ; 2.43 (dd, IH) ; 1.52 (m, 2H) ; 1.32 (m, 2H) ; 0.88 (t, 3H) . Part F: Methvl-N^-n-buty!oxyoarbonyl-N 3 -- T3- (4- a idinophenvl) isoxazol n-5 (S) -ylacetyl!- (S) -2.3- diaminopropionate TFA salt. To a solution of methyl-N 2 -n-butyloxycarbonyl-N 3 - [3- (4-cyanophenyl) isoxazolin-5 (S)-ylacetyl]- (S)-2,3- diaminopropionate (4.4 mmol, 1.9 g) in 50 mL methanol was bubbled with HCI gas at 0°C for 1 hour and the solution was stirred at room temperature for 5 hours and concentrated. The residue was taken up in 20 mL methanol and ammonium carbonate (11 mmol, 1.1 g) was added. The mixture was stirred at room temperature overnight and concentrated. The solid was dissolved in methanol/water/TFA and purification on reversed phase HPLC gave 1.0 g (40%) product. ESI (M+H) + : Calcd 448.3; Found 448.3. Example 314B Methyl-N^-n-butyloxycarbony1-N 3 -- .3- (4- amidinophenyl) isoxazolin-5 (R) -ylacetyl!- (S)-2.3- dia inopropionate TFA salt Part A: 3- (4-oyanophenyl)-5 (R)-ylacetic acid This material was resolved from 3-(4- cyanophenyl) isoxazolin-5(ft, S)-ylacetic acid as described above in the proceudure for Example 314A, Part E. Part B: Methyl-N^-n-butyloxycarbonyl-N 3 -- T3- (4- cyanpphenyl)ispχazplin-5( )-ylacetyl1-fS)- .3- diaminopropionate. This material was synthesized from 3- (4- cyanophenyl)-5 (R) -ylacetic acid (4.3 mmol, 1.0 g) , Methyl N 2 -butyloxycarbonyl- (S) -2,3-diaminopropionate TFA salt (5 mmol, 1.27 g) , BOP (4.5 mmol, 2 g) and diisopropylethylamine (16 mmol, 2.8 L) using the same procedure as for XVI. Yield 1.75 g (95%) . NMR (DMSO-d δ ) : δ 8.12 (t, IH); 7.94 (d, 2H) ; 7.83 (d, 2H) ; 7.46 (d, IH) ; 5.04 (m, IH) ; 4.16 (m, IH) ; 3.96 (t, 2H) ; 3.64 (s, 3H) ; 3.58 (dd, IH) ; 3.40 (m, 2H) ; 3.20 (dd, IH) ; 2.56 (dd, IH) ; 2.43 (dd, IH) ; 1.52 (m, 2H) ; 1.32 (m, 2H) ; 0.88 (t, 3H) . Part C: Methvl-N^-n-butvloxvcarbonyl-N 3 -- .3- (4- amidinophenyl) isoxazolin- (R) -ylacetyl 1- (S)-2. - diaminopropionate TFA salt This compound was synthesized from Methyl-N 2 -n- butyloxycarbonyl-N 3 - [3- (4-cyanophenyl) isoxazolin-5 (R) - ylacetyl]-(S)-2,3-diaminopropionate (4.0 mmol, 1.7 g) using the same procedure as for Example 314A, Part G. Yield 1.0 g (45%) . ESI (M+H) + : Calcd 448.3; Found 448.3. Example 344 Methyl (ft)-f5 (ft. S) -N-f3- (4-Amidinophenvl) isoxazolin-5- ylacety11amino!heptanoate Part A. (E) -Methyl 2-heptenoate To a solution of diethyl methylphosphonoacetate (19 ml, 104 mmol) in dry THF (800 ml) at -4 °C was added 64 ml of n-BuLi (1.6 M in hexane, 102 mmol) dropwise over 45 min. The resulting solution was stirred 1 h at room temp. Valeraldehyle (10.0 ml, 94 mmol) was added and stirred 3.5 h at room temp. The reaction was quenched with 25 ml sat. NH 4 CI. Solvents were distilled at atmospheric pressure, and the resulting solids were taken up in EtOAc, extracted with water and brine, and dried with Na 2 S0 4 . The solvents were again distilled at atmospheric pressure, and the resulting yellow liquid was distilled under house vacuum to yield 7.2 g clear liquid, boiling range under house vacuum 90-125 °C; HRMS, e/z Calc. for (M+H) + : 143.1072. Found: 143.1070; IR(film) 1728, 1658 cm -1 . Part B. N- (1- (ft) -1-Phenylethyl )benzamide A solution of benzoyl chloride (22.5 mL, 0.19 mole) in dichloromethane (10 mL) was added dropwise over 1.5 h to a 0 °C solution of (ft)-(+)-α-methylbenzylamine (25 mL, 0.19 mole), triethylamine (31 mL, 0.22 mole), and 4- DMAP (100 mg) , in dichloromethane (1 L) . After 1.75 h at 0 °C the mixture was concentrated in vacuo, then diluted with EtOAc. This mixture was extracted with water, 1 M HCI, water, and brine, then dried (MgSθ 4 ) and concentrated to yield 43.4 g of a colorless crystalline solid; mp 121.0-121.5 °C; IR(KBr) 3332, 1636 cm -1 ; [α] D 25 -2.30° (c=1.002, CH 2 CI 2 ) ; Anal. Calc. for C 1 5H 15 NO: C, 79.97; H, 6.71; N, 6.22. Found: C, 79.88; H, 6.65; N, 6.17. Part C. N- (1- (ft)-1-Phenylethyl) -Λt-henzy mine BH3/THF (1 Λf in THF, 220 mL, 220 mmol) was added dropwise over 1 h to a 0 °C solution of the above benzamide (20 g, 89 mmol) in dry THF (200 mL) . The ice bath was removed, and the mixture was heated to reflux for 40 h. A TLC analysis indicated incomplete reaction, so more BH3/THF (1 M in THF, 30 mL, 30 mmol) was added, and heating resumed for 22.5 h. After cooling, MeOH (250 mL) was added dropwise cautiously over 5 h. The resulting mixture was boiled for 2 h, then cooled and concentrated in vacuo . Reconcentration from MeOH (2 x 500 mL) and drying under high vacuum gave 19.3 g of an oil containing a small amount of a precipitate. This crude product was stirred with hot 2 Λf HCI (140 mL) to generate a clear solution, then slowly cooled to RT, and ultimately in an ice bath to yield a crystalline solid, as described by Simpkins ( Tetrahedron 1990, 46 (2 ) , 523) . The solid was collected by filtration and rinsed with a small amount of water. After air drying for 3 d, 16.35 g of the hydrochloride salt was obtained; mp 178.5- 179.5 °C; [α] D 21 +18/9° (c=4.0, EtOH) . The salt was converted to the free base by extraction with Et2θ and aq. KOH, then Kugelrohr distilled, oven temp. 120-140 °C (1.1 mm Hg) to give 12.5 g of an oil; [α] D 21 +61.2° (c=3.98, EtOH); Anal. Calc. for C 1 5H 17 N: C, 85.26; H, 8.11; N, 6.63. Found: C, 84.93; H, 7.75; N, 6.58. Part D. Methyl 3- (R)-f -benzyl- -(1- (R)-1- phenylethyl)amino!heptanoate Following the asymmetric Michael addition method of Davies ( Tetrahedron . -Asymmetry 1991, 2(3), 183), n- butyllithium (1.6 Λf in hexanes, 4.4 mL, 7.0 mmol) was added dropwise over 3 min to a 0 °C solution of N- ( l- (ft) -l-phenylethyl) -N-benzylamine (1.5 g, 7.0 mmol) in dry THF (35 mL) . After 30 min, the resulting dark pinkish-red solution was cooled to -78 °C, and a solution of methyl 2-heptenoate (0.50 g, 3.5 mmol) in THF (10 mL) was added dropwise over 10 min. After 13 min, the cold reaction was quenched with saturated ΝH 4 CI (7 mL) . After warming to RT, the mixture was extracted with Et 2 θ and brine, dried (MgSθ 4 ) , and concentrated in vacuo . The product was purified by chromatography over silica gel, eluting with 0% to 50% EtOAc in hexane. The cleanest major product fractions (apart from a few mixed fractions) were concentrated in vacuo to give 0.91 g of a pale yellow oil which by NMR is a single diastereomer, with the newly generated asymmetric center assigned as 3(ft) by analogy with the Davies reference above; 13 C NMR (300 MHz, CDCI 3 ) δ 173.31, 143.40, 141.78, 128.40, 128.27, 128.11, 128.00, 126.91, 126.67, 57.90, 54.22, 51.32, 50.05, 36.83, 33.28, 29.32, 22.72, 19.40, 14.12; [α] D 25 +12.96° (c=0.602, MeOH) . Part E. Methyl 3- (ft)-aminoheptanoate » acetic acid salt Methyl 3-(ft)- [N-benzyl-N- (1- (ft)-1- phenylethyl)amino]heptanoate (0.70 g, 2.0 mmol), 20% Pd(OH)2/C (0.35 g) , cyclohexene (7 mL) , glacial HOAc (0.12 mL, 2.1 mmol), and MeOH (14 mL) were heated at reflux under Ν2 for 20.5 h. After cooling, the catalyst was removed by filtration thru a Celite plug, rinsed with MeOH, and the solution concentrated in vacuo . Drying overnight under high vacuum yielded 0.43 g of a viscous oil; 13 C NMR (300 MHz, CDCI3) δ 177.64, 171.52, 51.97, 48.22, 37.24, 33.08, 27.50, 23.31, 22.29, 13.76; [α] D 25 -10.6° (c=0.602, MeOH) . Part F. Methyl 3 (ft)-f5 (ft..<?) -At- L3- (4- cyanophenyl) isoxazolin-5-ylacetyl1amino!heptanoate To a suspension of 3- (4-cyanophenyl) isoxazolin-5- ylacetic acid (300 mg, 1.3 mmol) in EtOAc (10 ml) was added methyl 3- (ft) -aminoheptanoate acetic acid salt (287 mg, 1.3 mmol), TBTU (420 mg, 1.3 mmol), and Et3N (600 μl, 4.3 mmol) . After stirring at room temp 2.5 h, the reaction mixture was extracted with 5% KHSO4, sat NaHCθ3, and brine, then dried with Na2Sθ4. Evaporation, followed by chromatography over silica gel in 50-100% EtOAc/hexanes yielded 245 mg colorless glass. MS (NH3- DCI) Calc. for (M+H) + : 372, (M+NH 4 ) + : 389. Found: 372, 389. Part G. Methyl 3 (ft)-(5 (ft. S) -N- 3- ( 4- Amidinophenyl) isoxazolin-5-ylacetyl 1 amino!heptanoate To a solution of methyl 3 (ft)-{5 (ft, S) -N- [3- (4- cyanophenyl) isoxazolin-5-ylacetyl]amino}heptanoate (179 mg, .48 mmol) in 15 ml dry MeOH at 0 °C, was added a stream of HCI gas generated from dropping two 20 ml portions of H2SO4 into solid NaCl over 35 min. After stirring 20 h at room temp, the solvent was removed with a rapid stream of N2. Et2θ was added and removed with a rapid stream of N2. The resulting gummy oil was taken up in 15 ml dry MeOH, to which was added (NH4)2Cθ3 (l.lg, 11.4 mmol) . After stirring 19.5 h at room temp, the solvent was removed with a rapid stream of N2, and the resulting white solid was purified by chromatography over silica gel, eluting with 0-20% MeOH/CHCl3. Purified product was taken up in 5% MeOH/CHCl3 and filtered. Concentration of the filtrate yielded 100 mg white solid. IR(KBr) 3600-2800, 1734, 1676, 1640 cm -1 ; HRMS, e/z Calc. for (M+H) + : 389.2189. Found: 389.2192. Example 348 Ethvl 3(ft)-{5(ft.£)-N-r3-(4-amidinophenyl) i soxazol n-5- vlacetvllaminol-5-methylhexanoate » trifluoroace ic acid salt Part A. (E)-Ethyl 5-methyl-?-hexenoate Prepared in analogous fashion to methyl 2- heptenoate, using triethyl phosphonoacetate, stirring 17 h at room temp upon addition of isovaleraldehyde. Distillation under house vacuum yielded 72% clear oil, boiling range under house vacuum 80-130 °C; IR(film) 1724, 1656 cm" ! . Part B. Ethvl 3- (ft) - rAt-henzyl -Λt- ( l - (ft) -l- phenvlethvl)amino!-5-methylhexanoate Prepared in analogous fashion via the asymmetric Michael addition of Ex. 344, part D above. Yield a viscous pale yellow oil (65%); 13 C NMR (300 MHz, CDCI3) δ 172.83, 143.56, 142.17, 128.27, 128.21, 128.15, 128.03, 126.96, 126.60, 60.10, 58.56, 52.43, 50.09, 43.23, 36.72, 24.76, 23.48, 22.13, 20.20, 14.21; [α] D 25 +5.12° (c=0.606, EtOH) . Part C. Ethyl 3-(fl)-amino-5-methylhexanpf_te • acetic acid salt Prepared as previously described except EtOH was used as solvent. Yield a waxy solid (94%); mp 57-61 °C; HRMS, e/z Calc. for (M+H) + : 174.1494. Found: 174.1485. Part D . Ethyl 3- (fi) -aπ_ino-5-methylhexanpate * hydrochloric arid salt The above acetic acid salt (1.1 g, 4.7 mmol) was stirred 4 min in 4 Λf HCl/dioxane (5.0 ml) . The resulting solution was triturated with Et 2 θ, cooled, and the clear liquid decanted, leaving an orange oil which solidified to 960 mg waxy solid on high vacuum; i H NMR (300 MHz, CDCI3) d 8.49 (br, 3H) , 4.20 (q, J = 7.3, 2H) , 3.70-3.65 (m, IH) , 2.86-2.80 (m, 2H) , 1.83-1.80 (m, 2H) , 1.58-1.54 (m, IH) , 1.30-1.26 (t, J = 7.3, 3H) , 0.99-0.91 (m, 6H) . Part E. Ethyl 3 (ft)-f5 (ft. <?) -N- r.3- (4- (N-t- butoxycarbonylamidino)phenyl) isoxazolin-5- ylaoetyllamino1-5-methyl exanoate To a suspension of 3- [ 4- (N-t- butoxycarbonylamidino)phenyl] isoxazolin-5-ylacetic acid (78 mg, 0.22 mmol) in EtOAc (5 ml) was added ethyl 3- (ft)-amino-5-methylhexanoate hydrochloride salt (47 mg, 0.22 mmol), TBTU (72 mg, 0.22 mmol), and Et 3 Ν (100 μl, 0.72 mmol) . After stirring 6 h at room temp, the reaction mixture was extracted with pH 4 buffer (potassium hydrogen phthalate) , sat NaHC03, and brine, then dried with Na2Sθ 4 . Evaporation, followed by chromatography over silica gel in 100% EtOAc yielded 33 mg colorless glass; i H NMR (300 MHz, CDCI3) 3 7.90 (d, J = 8.4, 2H), 7.70 (dd, J = 8.5, J' = 1.9, 2H) , 6.32-6.28 (m, IH), 5.13-5.11 (m, IH) , 4.34-4.33 (m, IH) , 4.17-4.09 (m, 2H), 3.56-3.47 (m, IH) , 3.25-3.17 (m, IH) , 2.71-2.46 (m, 4H) , 1.66-1.47 (m, 2H) , 1.56 (s, 9H) , 1.31-1.23 (m, 4H) , 0.92 (dd, J = 6.6, J' = 1.8, 3H) , 0.84 (d, J = 6.6, 3H) . Part F. Ethyl 3 (ft) -(5 (ft..?) -N- .3- ( 4- amidinophenyl) isoxazolin-5-ylacetyl! amino1-5-methyl hexanoate * trifluprpacetic acid salt The product from Part E above (29 mg, 0.058 mmol) was dissolved in DCM (300 μl) , to which was added TFA (100 μl) . The resulting solution was stirred at room temp under a CaSθ4 drying tube for 3.5 h, and triturated with Et2°. 24 mg white solid were collected by filtration; iH NMR (300 MHz, CDCI3) 3 9.4 (br, IH) , 9.0 (br, IH) , 7.8 (s, 4H) , 5.0 (m, IH) , 4.2 (m, IH) , 4.0 (q, 2H) , 3.6 (m, IH) , 3.3 (m, 2H) , 2.4 (m, 3H) , 1.6 (m, IH) , 1.4 (m, IH) , 1.2 (m, 4H) , 0.8 (m, 6H) ; HRMS, e/z Calc. for (M+H) + : 403.2345. Found: 403.2363. Example 35Q Methyl 3 (ft..9)- 5 (ft. <?) -N- T3- (4-amidinophenyl ) i soxazolin- 5-ylacetyl1aminp}-4-(phenylthip)butanpate • hydrochloric acid salt; Part A. Methyl phenylthioacetoacetate To a solution of thiophenol (5.00 ml, 48.6 mmol) in DMF (20 ml), K2CO3 (10.09 g, 73 mmol) and methyl chloroacetoacetate (5.93ml, 48.6 mmol) were added. The reaction mixture was stirred 6 h at 50 °C, diluted with EtOAc, and extracted with saturated Na2Sθ , water, and brine, then dried (Na2Sθ4) and concentrated. The resulting oil was chromatographed with 20% EtOAc in Hexane to yield 9.40 g yellow oil; MS (CH4-DCI) Calc. for (M+H) + : 224. Found: 224; IR(KBr) 2954,1656,1438, 626 cm -1 . Part B. Methyl-3 (ft. S) -amino-4-phenylthiobutanoate To a solution of methyl phenylthioacetoacetate (1.00 g, 4.5 mmol) in MeOH (20 ml), ammonium formate (4.26 g, 6.75 mmol) and sodium cyanoborohydride (0.42 g, 6.7 mmol) were added. The reaction mixture was stirred at room temperature for 18 h, then diluted with EtOAc and partitioned into 1 Λf HCI. The aqueous layer was then basified to pH = 8.0 with NaOH. The desired product was extracted out with EtOAc, washed with water and brine, dried over Na2S0 4 and concentrated to yield 0.61 g yellow oil; MS (NH3-CI/DDIP) Calc. for (M+H) + : 226. Found: 226; i H NMR (300 MHz, CDCI3) δ 7.39 (d, J = 7, 2H) , 7.32-7.26 (m, 3H) , 7.22 (d, J = 10, IH) , 3.74 (s, 3H), 3.39-3.31 (m, IH) , 3.13-3.07 (dd, J = 13, J' = 9, IH) , 2.91-2.83 (dd, J = 12, J' = 6, IH) , 2.65-2.58 (dd, J = 12, J 1 = 6, IH), 2.46-2.38 (dd, J = 16, J' = 8, IH) . Part C. Methvl-3 (ft..9) -(5 (ft. S) -N- L3- (4-cyanophen- yl) isoxazolin-5- ylacetyl 1amino!-4- (pheny!thio)butanoate To a suspension of 3- (4-cyanophenyl) isoxazolin-5- ylacetic acid (0.50 g, 2 mmol) in EtOAc (10 ml), methyl- 3 (ft, S)amino-4- (phenylthio)butanoate (0.51 g, 2 mmol), TBTU (0.71 g, 2 mmol), and Et3N (1.24 ml, 8.9 mmol) were added. The reaction mixture was stirred 2 h at room temperature, diluted with EtOAc, washed with 5% citric acid, saturated NaHC03, and brine, dried over Na 2 S0 4 , concentrated, and the resulting oil was chromatographed over silica gel in 100% EtOAc to yield 0.61 g of a yellow glass: MS ' H3-CI/DDIP) Calc. for (M+H) + : 438.1. Found: 436 ; Anal. Calc. for C32H 2 3N3O 4 S 1 : C, 63.31; H, 5.30; N, .60; S, 7.33. Found: C, 62.99; H, 5.22; N, 9.53; S, 7.30. Part D. Methyl 3 (ft..9)-f5 (R..9) -At- L3- 14- amidinophenvl) isoxazolin-5-vlacetyl 1 amino!-4- (phenylthio)butanoate » hydrochloric acid salt The product from Part C above (0.30 g,0.68 mmol) was dissolved in dry MeOH (20 ml) at 0 °C. To the resulting solution, HCI gas was bubbled in from a generator as described in Example 344, Part G, over a period of 2 h. The generator was removed and the reaction mixture stirred at 0 °C for 18 h, then concentrated and triturated with CHCI3. The resulting precipitate was collected by filtration and redissolved in dry MeOH (20 ml) . To this solution, ammonium carbonate (0.99 g, 10 mmol) was added and the mixture stirred at room temperature for 18 h. The solution was concentrated and recrystallized from DCM/MeOH to yield 0.14 g white solid; HRMS, e/z Calc. for (M+H) + : 455.1753. Found: 455.175; iH NMR (300 MHz, d 6 -DMSO) δ 9.44 (br S,1H), 9.18 (br s, IH) , 8.22 (d, J = 10, IH) , 7.86 (m, 4H) , 7.41-7.25 (m, 4H) , 7.2 (m, IH) , 5.03 (m, IH) , 4.2 (m, IH) , 3.59 (s, 3H) , 3.29-3.05 (m, 4H) , 2.8- 2.39 (m, 4H) . Example 359 Methyl 3 (ft..9)-f5 (ft..9) -At- T3- (4-amidinophenyl ) i oxazolin- 5-ylacetyllaminol-4- (phenylsulfonamido)butanoate » trifluprpacetic acid salt; Part A. Methyl 3- (ft. S) -hydroxy-4-aminobutanoate » hydrochloric acid salt Chlorotrimethylsilane (100 mL, 0.79 mol) was added dropwise over 1.5 h to a stirred 0 °C suspension of 4- amino-3- (ft, S) -hydroxybutyric acid (25 g, 0.21 mol) in MeOH (1 L) . The resulting clear solution was allowed to slowly warm to room temperature overnight. The solvent was evaporated in vacuo, and the resulting residue was reconcentrated from more MeOH (2 x 500 mL) . Drying under high vacuum produced 37 g of a viscous oil; 13 C NMR (300 MHz, d6~DMSO) δ 171.42, 90.14, 64.67, 51.89, 44.39; Anal. Calc. for C5H 1 6CINO3: C, 35.41; H, 7.13; N, 8.26; Cl, 20.90. Found: C, 35.18; H, 7.09; N, 8.18; Cl, 20.77. Part B. Methyl 3- (ft..9)-hydroxy-4- (phenylsulfonamido)butanoate A solution of benzenesulfonyl chloride (7.5 mL, 59 mmol) in dichloromethane (10 mL) was added dropwise over 55 min to a 0 °C solution of the Part A amine salt (10 g, 50 mmol), and Et3N (17 mL, 120 mmol) in dichloromethane (110 mL) . The mixture was allowed to slowly warm to room temperature, and stirring was continued over the weekend. After solvent removal in vacuo, the mixture was diluted with EtOAc and extracted with H 2 O, 0.1 Λf HCI, and brine. Drying (MgS0 4 ) and solvent removal in vacuo yielded 14.6 g of a viscous oil; 13 C NMR (300 MHz, CDCI3) δ 172.67, 139.79, 132.78, 129.22, 127.02, 66.77, 52.01, 47.72, 38.31; Anal. Calc . for C11H15NO5S : C, 48 . 34 ; H, 5 . 53 ; N, 5 . 13 ; S , 11 . 73 . Found : C , 48 . 44 ; H, 5 . 61 ; N, 4 . 90 ; S , 11 .34 . Part C. Methyl 3-oxo-4- (phenylsulfonamido)butanoate The Part B alcohol (2.8 g, 10 mmol) was oxidized with Jones reagent under standard conditions. The ketone was purified by chromatography on silica gel, eluting with 0% to 100% EtOAc in hexane, to yield 1.11 g of a waxy solid; mp 94.5-95.5 °C; 13 C NMR (300 MHz, CDCI3) δ 197.08, 166.80, 139.17, 133.08, 129.29, 127.17, 52.71, 51.91, 46.15; Anal. Calc. for C 11 H 1 3NO 5 S: C, 48.70; H, 4.83; N, 5.16; S, 11.82. Found: C, 48.77; H, 4.69; N, 5.08; S, 11.88. Part D. Methyl 3-(fl,g)-3-amino-4- (phenyl ulfonami o)butanoate To a room temperature solution of the Part C ketone (0.71 g, 2.6 mmol) in MeOH (7 mL) and THF (3 mL) was added ammonium formate (2.5 g, 39 mmol) and sodium cyanoborohydride (0.25 g, 3.9 mmol) . After 45.5 h, solvent was evaporated, and the residue was diluted with EtOAc (70 mL) . This solution was extracted with 1.0 Λf NaOH, H 2 O, and brine. After concentration, the product was purified by chromatography on silica gel, eluting with 0% to 100% EtOAc in hexane, then 1% to 20% MeOH in EtOAc to yield 0.16 g of a viscous oil, which eventually solidified; i H NMR (300 MHz, CDCI3) 3 9.79 (br, 2H) , 7.84 (d, 2H, J = 8 Hz), 7.81 (br, IH) , 7.68-7.53 (m, 3H) , 4.05-3.92 (m, IH) , 3.75 (s, 3H) , 3.33-3.17 (m, 2H) , 2.89-2.72 (m, 2H) ; HRMS, e/z Calc. for (M+H) + : 273.0909. Found: 273.0916. Part E. Methyl 3- (R,.?)-f5 f R, S) ~N- \ X ( .- (N-X butoxycarbonvlamidino) phenyl ) isoxazolin-5- ylacetyπaminp}-4-(phenylsulfpnamido)butanoate This compound was prepared analogous to Example 348, Part E, stirring 24 h in 5 ml EtOAc and 1 ml DMF. Chromatography in 5% MeOH/CHCl 3 yielded 80% of an orange solid; IR(KBr) 3296, 2338, 1736, 1660, 1618 cm "1 ; HRMS, e/z Calc. for (M+H) + : 602.2285. Found: 602.2270. Part F. Methyl 3 (ft..9) -(5 (R..9) -At- L3- (4- amidinophenyl) isoxazolin-5-ylacetyll aminol-4- (phenylsulfonamido)butanoate « trifluoroacetic acid salt The product from Part E was deprotected analogously to Example 348, Part F, yielding 86% pink solid; IR(KBr) 3312, 3104, 1734, 1670; HRMS, e/z Calc. for (M+H) + : 502.1760. Found: 502.1761. The more active diastereomer (based on PRP assay) was isolated from the above mixture by SFC HPLC, Chiralpak AD - 2X25 cm, eluted with 0.1% TFA/25% MeOH/75% CO2. Under these conditions, the more active diastereomer eluted last. Example 362 Methyl 3 (ft. .9) - f 5 (ft. .9) -N- r3- (4-amidinophenyl ) i oxazolin- 5-ylacetyl!aminol-4- (n-butylsulfonamido)butanoate ■ trifluprpacetic acid salt; Part A. Methyl 3- (ft..9)-hydroxy-4- (n- butylsulfonamido)butanoate This compound was prepared entirely analogously to Ex.359, Part B, using n-butylsulfonylchloride instead. A colorless, waxy solid of excellent purity was obtained in 65% yield without purification; mp 46-50 °C; 13 C NMR (300 MHz, CDCI3) δ 172.64, 67.29, 52.56, 51.99, 47.83, 38.40, 25.57, 21.52, 13.55; Anal. Calc. for C9H19NO5S: C 42.67; H, 7.56; N, 5.53; S, 12.66. Found: C, 42.69; H, 7.59; N, 5.36; S, 12.78. Part B. Methyl 3-oxo-4- (n-butylsulfonamido)butanoate The immediately preceeding alcohol was oxidized as described for Example 359, Part C, to give a 57% yield of a colorless solid; mp 53-55 °C; Anal. Calc. for C9H 17 NO5S: C, 43.02; H, 6.82; N, 5.57; S, 12.76. Found: C, 42.68; H, 7.03; N, 5.'74; S, 13.06. Part C. Methyl 3 (ft..9)-3-amino-4- i - butylsulfonamido)butanoate This compound was prepared analogous to Example 350, Part B, using the product from Part B above (1.20 g, 4.8 mmol) yielding 0.26 g yellow oil; IH NMR (300 MHz, CDCI3) δ3.70 (s, 3H) , 3.38 (m, IH) , 3.24-3.13 (m, IH) , 3.02 (m, 4H) , 2.58-2.52 (dd, J = 16, J' = 11, IH) , 1.79 (m, 2H) , 1.24 (m, 2H) , 0.95 (t, 3H) ; MS (NH4-DCI) Calc. for (M+H) + : 271. Found: 271. Part D. Methyl-3 (ft. S) -(5 (ft..9) -N- \3- (4- (N-t- butoxvcarbonvlamidine) phenyl) isoxazolin-5- vlacetvl!aminol-4-(n-butvlsulfonylamido)butanoate To a solution 3- [4- (N-t- butoxycarbonylamidine)phenyl]isoxazolin-5-ylacetic acid (0.24 g, 0.83 mmol) in DMF (20 ml), the product from Part C above (0.29 gr, 0.83 mmol), TBTU (0.27 g, 0.83 mmol), and Et3N (0.46 ml, 3.3 mmol) was added. After stirring 4 h at room temperature, the reaction mixture was diluted with EtOAc, extracted with pH 4 buffer (potassium hydrogen phthalate) , saturated NaHC0 3 , brine, then dried (NaS0 4 ) . Concentration, followed by chromatography over silica gel in 100% EtOAc, yielded 1.17 g of a white foam; MS (NH3-DCI) Calc. for (M+H) + : 582.3. Found: 582; IR(KBr) 3312, 2338, 1620, 1144 cm " 1. Part E. Methyl 3 (ft. S) -(5 (ft..9) -N- 3- (4- amidinophenyl) isoxazolin-5-ylacetyllamino!-4- (n- butylsulfonylamido)butanoate » trifluoroacetic acid To a solution of the product from Part D above (0.22 g, 0.37 mmol) in DCM (10 ml) ' , trifluoroacetic acid (2.2 ml) was added. The reaction mixture was stirred 2 h at room temperature, triturated with Et2θ, and the resulting precipitate was chromatographed over silica gel in 20% MeOH in CHCI3 to yield 0.20 g white solid; HRMS, e/z Calc. for (M+H) + : 482.2073. Found: 482.2090; mp = 178-184 °C. Exa ple 365 Methyl (5 (ft..9) - t- T3- (4-amidinopheny1 ) isoxazol in-5- ylacetyl l minol-4- (methoxycarbonyl)butanoate • trifluoroacetic acid salt: Part A. Dimethyl 3-aminoglutarate • hydrochloric acid salt This product was prepared similarly to Example 359, Part A, from β-glutamic acid to yield the diester as a colorless gum in quantitative yield; HRMS, e/z Calc. for (M+H) + : 176.0923. Found: 176.0933. Part B. Methyl (5 (ft..9) -At- T3- (4- (A7-t- butoxycarbonylamidino)phenyl) isoxazolin-5- vlacetvllaminol-4- (methoxycarbonyl)butanoate Prepared analogous to Example 359, Part E, to yield 32% of a white solid; IR(KBr) 3306, 2338, 1738, 1656, 1620 cm -1 ; HRMS, e/z Calc. for (M+H) + : 505.2298. Found: 505.2283. Part C. Methyl (5 (ft..9) -At-f3- (4- amidinophenyl) isoxazolin-5-ylacetyllaminol-4- (methoxycarbonyl)butanoate * trifluoroacetic acid salt Prepared analogous to Example 348, Part F, yielding 83% white solid; IR(KBr) 3316, 3102, 2340, 1736, 1670 cm -1 ; HRMS, e/z Calc. for (M+H) + : 405.1774. Found: 405.1775. Example 368 Methyl 3 ( R. .9) - r5 (R . .9) -At- r 3- ( 4-amidi nopheny! ) isoxa olin- 5-ylacetyllaminol-4-(methoxyr:arhonyl ) entanoate • trifluoroacetic acid salt: Part A. Dimethyl 3- (ft f S)-aminoadipate » hydrochloric acid salt This product was prepared as in Example 359, Part A, from β-aminoadipic acid to yield a colorless gum in quantitative yield; HRMS, e/z Calc. for (M+H) + : 190.1079. Found: 190.1080. Part B. Methvl-3 (ft..9) -(5 (ft..9) -At- .3- (4- ( N- - hutoxvcarhonylamidine) phenyl ) i soxzal in-5- ylacetyllamino)-4- (methoxycarbonyl) pentanoate This product was prepared similarly as in Example 362, Part D, using the product from Part B above (0.70 g, 3.1 mmol) instead to yield 1.17 g of a white foam; HRMS, e/z Calc. for (M+H) + : 519.2454. Found: 519.2459; Anal. Calc. for C25H34N4O8 : C, 57.90; H, 6.61; N,10.80. Found: C, 57.73; H, 6.51; N, 10.86. Part C. Methvl-3 (ft..9) -(5 (ft..9) -N- T3- (4- amidinophenyl) isoxazol n-5-ylacety 1 mine1-4- (methoxyacarbonyl)pentanoate » trifluoroace ic acid salt This product was prepared as in Example 362, Part E, using the product from Part C above (1.00 g, 1.9 mmol) to yield 0.9 g white solid; HRMS, e/z Calc. for (M+H) + : 419.1930. Found: 419.1921; mp = 214-215 °C (decomposes) . Exampl 375 Preparation of 2- (R. S)-2-Carboxymethyl-l-J5- (R. S)-A7- T3- (4-amidinophenyl) isoxazolin-5-yl acetyl! Ipiperidine Part A. Preparation of 2- (Methoxy-2-oxoethyl)piperidine Pyridylacetic acid hydrochloride (10.00 g, 57.6 mmol) and platinum(IV) oxide (1.00 g, 4.4 mmol) were shaken in a mixture of 75 ml acetic acid, 75 ml methanol, and 10 ml cone. HCI on Parr under 60 psi hydrogen at room temperature overnight. The mixture was then filtered through Celite, and the filtrate evaporated under reduced pressure to yield 8.42 g (75.9%) of the title compound as an off-white solid. MS (NH3-CI/DDIP) : m/e 158 (M+H) + . i H NMR (300 MHz, CDCI3) : δ 1.50-1.96 (m, 6H) ; 2.80 (m, 2H) ; 3.20-3.60 (m, 3H) ; 3.76 (s, 3H) . 13 C NMR (60 MHz, d 6 -DMSO) : 521.94; 28.05; 37.46; 40.49; 44.12; 57.33; 52.74; 170.39. Part B. Preparation of 2- (R, S)-2- (Methoxy-2-oxoethyl) - 1-{5-(R,S) -N- [3- (4-cyanophenyl) isoxazolin-5-yl acetyl] }piperidine To 2.00 g (8.69 mmol) of 3- (4-cyanophenyl)- isoxazolin-5-yl acetic acid in 100 ml anhydrous DMF was added 1.36 g (8.69 mmol) of 2- (methoxy-2- oxoethyl)piperidine, 2.80 g (8.69 mmol) of TBTU, and 6.05 ml (34.7 mmol) of diisopropylethylamine. After stirring for 6 hrs, the reaction mixture was diluted with ethyl acetate and washed with 5% aqueous citric acid solution, water, 5% aqueous ΝaHCθ3 solution, and saturated NaCl solution. The organic layer was dried over Na 2 Sθ 4 and filtered. The filtrate was evaporated under reduced pressure to give the crude product as a yellow foam. Purification by flash column chromatography on silica gel using 25-75% ethyl acetate in hexane yielded 1.54 g (48%) of the title compound as a yellow foam. One diastereomer (racemic) was isolated from the mixture. MS (NH3-CI/DDIP) : m/e 370 (M+H) + . i H NMR (300 MHz, CDCI3) : δ 1.42-1.76 (m, 6H) ; 2.60 (m, 2H) ; 2.77- 3.01 (m, 3H) ; 3.05-3.26 (m, 2H) ; 3.56-3.70 (m, 4H) ; 4.50 (m, IH) ; 5.20 (m, IH) ; 7.69 (d, J = 8.4 Hz, 2H) ; 7.77 (d, J = 8.4 Hz, 2H) . Part C. Preparation of 2- (Methoxy-2-oxoethyl) -1- {N- [3- (4-amidinophenyl) isoxazolin-5-yl acetyl] Jpiperidine, (racemic diastereomer A) HCI gas was bubbled for 2 hrs through a solution of 1.02 g (2.80 mmol) of the product of part B above in 30 ml of anhydrous MeOH cooled in an ice bath. The reaction flask was then sealed with Teflon tape and warmed to room temperature while stirring overnight . MeOH was evaporated under reduced pressure and then under vacuum to give the intermediate imidate as a yellow foam. MS (ESI) : m/e 402 (M+H) + . It was then stirred with 8.07 g (84.0 mmol) of (NH 4 ) 2 C0 3 in 30 ml anhydrous EtOH overnight in a sealed reaction flask. After filtering, the filtrate was evaporated under reduced pressure to give the crude product as a yellow foam, which was then purified by flash column chromatography using 5-17% MeOH in CH 2 CI2 to give 0.29 g (26.8%) of the title compound as a yellow solid. MS (ESI) : m/e 387 (M+H) + . i H NMR (300 MHz, d 6 -DMSO) : δ 1.57-1.67 (br., 6H) ; 2.46-2.90 (m, 5H) ; 3.16 (m, 2H) ; 3.53-3.64 (m, 4H) ; 4.36 (br. m, IH) ; 5.07 (br. m, IH) ; 7.89 (m, 4H) ; 9.38 (br. s, 3H) . Part D. Preparation of 2-Carboxymethyl-l- {N- [3- (4- amidinophenyl) isoxazolin-5-yl acetyl] Jpiperidine, (Racemic Isomer A) To a solution of 0.08 g (0.2 mmol) of the product isolated in Part C above in 5 ml anhydrous THF at ambient temperature was added 0.5 ml (0.5 mmol) of 1.0 M solution of NaOTMS in THF. After stirring overnight, solvent was evaporated under reduced pressure to give a yellow solid, which was recrystallized from MeOH and Et2θ to give 0.05 g (64.9%) of the title compound as a yellow powder. MS (ESI) : m/e 373 (M+H) + . i H NMR (300 MHz, CD 3 OD) : 51.68 (br., 6H) ; 2.56 (m, 2H) ; 2.72 (m, 3H) ; 2.94 (m, 2H) ; 3.57 (m, 4H) ; 4.46 (br., IH) ; 5.18 (br., IH) ; 7.84 (m, 4H) . Example 377 Preparation of 2- (R.S)-2-Carboxγmethyl-l-f5- (R.S) -At- T3- (4-amidinophenγl) isoxazolin-5-yl acetyl! lazepine Part A. Preparation of 2- (R, S)-2- (Ethoxy-2-oxoethyl)-1- {5- (R,S) -N- [3- (4-cyanophenyl) isoxazolin-5-yl acetyl] Jazepine From 0.50 g (2.17 mmol) of 3- (4- cyanophenyl) isoxazolin-5-yl acetic acid, using 0.40 g (2.17 mmol) of 2- (ethoxy-2-oxoethyl) azepine, 0.70 g (2.17 mmol) TBTU, and 1.51 ml (8.70 mmol) diisopropylethylamine, 0.73 g (84.6 %) of the title compound was obtained following the procedure of Example 375, Part B. MS (NH 3 -CI/DDIP) : m/e 398 (M+H) + . i H NMR (300 MHz, CDCI3) : 51.26 (m, 11H) ; 1.83 (br., 2H) ; 2.05 (m, IH) ; 2.18-2.65 (m, 2H) ; 2.76-2.85 (m, IH) ; 3.04 (m, 2H) ; 3.62 (s, IH) ; 4.08 (m, 2H) ; 5.22 (m, IH) ; 7.68 (d, J = 8.4 Hz, 2H) ; 7.78 (d, J = 8.4 Hz, 2H) . Part B. Preparation of 2- (R, S)-2- (Ethoxy-2-oxoethyl)-1- {5- (R,S) -N- [3- (4-amidinophenyl) isoxazolin-5-yl acetyl] Jazepine From 0.73 g (1.84 mmol) of 2- (R,S)-2-(ethoxy-2- oxoethyl)-l-{5- (R,S) -N- [3- (4-cyanophenyl) isoxazolin-5-yl acetyl] }azepine, using EtOH as the solvent, 0.42 g (61.6%) of the title compound was obtained following the procedure of Example 375, Part C. MS (ΝH3-CI/DDIP) : m/e 415(M+H) + . i H NMR (300 MHz, d 6 -DMSO) : δ 1.18 (m, 3H) ; 1.38 (m, 2H) ; 1.70 (m, 4H) ; 2.08 (br. , 2H) ; 2.66 (m, 2H) ; 3.02-3.26 (m, 2H) ; 3.60 (br. m, 2H) ; 4.05 (m, 2H) ; 4.58 (m, IH) ; 5.10 (m, IH) ; 7.90 (m, 4H) ; 9.38 (br. s, 3H) . Part C. Preparation of 2- (R, S)-2-Carboxymethyl-l-{5- (R, S) -N- [3- (4-amidinophenyl) isoxazolin-5-yl acetyl] Jazepine From 0.16 g (0.35 mmol) of 2- (R,S)-2- (ethoxy-2- oxoethyl) -l- { 5- (R, S) -N- [3- (4-amidinophenyl) isoxazolin-5- yl acetyl] Jazepine and using 0.89 ml (0.89 mmol) of 1.0 M solution of ΝaOTMS in THF, 0.12 g (82.9%) of the title compound was obtained following the procedure of Example 375, Part D. MS (ΝH3-DCI) : m/e 387 (M+H) + . Example 400 Preparation of 3- (R. ) - (Methoxy-2-oxoethyl ) -4- f5- (R. )- N- r 3- ( 4-amidinophenvl ) isoxazolin-5-vl acetvl! loioerazin- 2-one Part A. Preparation of 3- (R, S)- (Ethoxy-2-oxoethyl)-4- {5- (R,S) -N-[3-(4-cyanophenyl) isoxazolin-5-yl acetyl] }piperazin-2-one From 1.00 g (4.34 mmol) of 3- (4- cyanophenyl) isoxazolin-5-yl acetic acid, using 0.81 g (4.34 mmol) of ethyl 2-piperazin-3-one acetate, 1.39 g (4.34 mmol) TBTU, and 3.02 ml (17.40 mmol) diisopropylethylamine, 1.08 g (62.4 %) of the title compound was obtained following the procedure of Example 375, Part B. MS (NH3-CI/DDIP) : m/e 399 (M+H) + . H NMR (300 MHz, CDCI3) : 51.26 (m, 3H) ; 2.71-3.65 (br., 9H) ; 3.87 (br. m, IH) ; 4.16 (m, 2H) ; 5.01 & 5.09 (two t, J = 5.0, 5.1 Hz, IH) ; 5.20 (m, IH) ; 7.00 & 7.12 (two br. , IH) ; 7.77 (m, 4H) . Part B. Preparation of 3- (R,S)-(Methoxy-2-oxoethyl)-4- {5-(R, S) -N- [3- (4-amidinophenyl) isoxazolin-5-yl acetyl] }piperazin-2-one From 1.08 g (2.71 mmol) of 3- (R,S) - (ethoxy-2- oxoethyl)-4-{5- (R,S) -N- [3- (4-cyanophenyl) isoxazolin-5-yl acetyl] }piperazin-2-one, 0.30 g (27.6%) of the title compound was obtained, following the procedure of Example 375, Part C. MS (ESI) : m/e 402 (M+H) + . X H ΝMR (300 MHz, d 6 -DMSO) : 52.70-3.67 (m, 12H) ; 3.91 (br., IH) ; 4.87 & 4.64 (two m, IH) ; 5.06 (m., IH) ; 7.88 (m, 4H) ; 8.16 (br., IH) ; 9.40 (br. s, 3H) . Example 434 Preparation of (S)-Νfl— T3- (4-Ami inophenyl )-i soxazolin-5- (R.S)-vlacetyll-α-aspart-Ν- (2-phenylethvl) amide. tri luoroacetic acid salt Part A. Preparation of (S)-Ν α - (Benzyloxycarbonyl)-β- (O- t-butyl)-α-aspart-N- (2-phenylethyl)amide To a solution of (S)-N- (Benzyloxycarbonyl)-β- (O-t- butyl)-aspartic acid (BACHEM-Bioscience Inc) (3.20 g, 9.9 mmol) in DCM (25 mL) , was added phenethylamine (1.34 g, 11.1 mmol); followed by DEC (2.10 g, 10.9 mmol) . The reaction mixture was stirred overnight at room temperature, affording a pale yellow solution. This solution was washed with water, IM HCI, 5% NaHC03 and sat. NaCl, dried over anhydrous MgS0 4 , filtered, and concentrated in vacuo to give 4.28 g (100%) of amide, which was of sufficient purity to be carried on to the next step; i H NMR (300 MHz, CDCI3) 5 7.35 (s, 5H) , 7.17-7.35 (bm, 5H) , 6.52 (bs, IH) , 5.93 (bd, J = 8.1 Hz, IH) , 5.10 (s, 2H) , 4.46 (bm, IH) , 3.50 (dd, J = 13.9,6.2 Hz, 2H) , 2.92 (dd, J = 17.0, 4.2 Hz, IH) , 2.78 (t, J = 7.1 Hz, 2H) , 2.57 (dd, J = 17.0, 6.4 Hz, IH) , 1.42 (s, 9H) ; Mass Spectrum (NH3-DCI, e/z, relative abundance) 444, (M+NH 4 ) + , 100%; 427, (M+H) + , 4%. Part B. Preparation of (S)-β- (O-t-butyl)-α-aspart-N- (2- phenylethyl)amide A solution of (S) -N- (benzyloxycarbonyl) -β- (O-t- butyl)-α-aspart-N- (2-phenylethyl)amide (4.09 g, 9.58 mmol) in ethyl alcohol (30 mL) was hydrogenated under atmospheric pressure using 10% palladium on carbon catalyst (1.0 g) for 90 minutes. The catalyst was filtered and the filtrate concentrated in vacuo to give 2.80 g of an amber oil, which was purified by flash chromatography (5% MeOH/DCM) , affording 2.13 g (76%)of the free amine as a solid product; i H NMR (300 MHz, CDCI3) 5 7.44(bs, IH), 7.20-7.35 (m, 5H) , 3.61 (dd, J = 8.4, 3.7 Hz, IH) , 3.52 (dd, J = 13.2, 7.0 Hz, IH) , 2.80- 2.90 (m, 3H) , 2.46 (dd, J = 16.7, 8.4 Hz, IH) , 1.58 (bs, 2H) , 1.45 (s, 9H) ; Mass Spectrum (ESI, e/z, relative abundance) 293, (M+H) + , 37%; 237, (M+H-C 4 H8) + , 100%. Part C. Preparation of Methyl 3-(4-methoxyiminophenyl)- (5R,S)-isoxazolin-5-ylacetate. Hydrochloride Salt A suspension of 3- (4-cyanophenyl)- (5R,S) - isoxazolin-5-ylacetic acid (23.1 g, 100 mmol) in 200 mL of anhydrous methanol was chilled in an ice bath and dry HC1 gas was bubbled through the reaction mixture until a clear solution was obtained. The total addition time was about three hours. The reaction flask was sealed and the reaction mixture was allowed to warm to room temperature, with stirring, over a period of about 24 hrs. At this point, the methanolic solution was poured into 600 mL of anhydrous ether, precipitating the product, and the resulting slurry was chilled to -25°C for 2 1/2 hours. The slurry was then diluted with an additional 100 mL of chilled anhydrous ether. The precipitate was filtered, washed with two 100 mL portions of chilled anhydrous ether, and suction dried under nitrogen to afford 23.3 g (73%) of the hydrochloride salt; H NMR (300 MHz, CDCI3) δ 12.9 (bs, IH) 12.2 (bs, IH) , 8.46 (d, J = 8.8 Hz, 2H) , 7.86 (d, J = 8.8 Hz, 2H) , 5.20 (bm, IH) , 4.59 (s, 3H) , 3.74 (s, 3H) , 3.53 (dd, J = 16.8, 10.6 Hz, IH) , 3.15 (dd, J = 16.8, 7.7 Hz, IH) , 2.90 (dd, J = 16.1, 6.2 Hz, IH) , 2.70 (dd, J = 16.1, 7.3 Hz, IH) , 1.77 (bs, IH) ; Mass Spectrum (NH 3 -CI/DDIP, e/z, relative abundance) 277, (M+H) + , 100%. Part D. Preparation of methyl 3- (4-amidinophenyl)- (5R,S)-isoxazolin-5-ylacetate . Hydrochloride Salt A suspension of methyl 3- (4-methoxyiminophenyl)- (5R,S)-isoxazolin-5-ylacetate hydrochloride (22.9 g, 73.0 mmol) in 500 mL of IM ammonia in anhydrous methanol was stirred at room temperature for 14 hours during which time all solids dissolved. The solution was concentrated in vacuo to give 22.1 g (100%) of crude hydrochloride salt as a tan solid; X H NMR (300 MHz, CDCI3) δ 9.6-9,2 (b) , 7.91 (d, J = 8.8, 2H) , 7.87 (d, J = 8.8, 2H) , 5.08 (bm, IH) , 3.64 (s, 3H) , 3.3-3.1 (m, 2H), 2.8 (m, 2H) ; Mass Spectrum (ESI, e/z, relative abundance) 264, (M+H) + , 100%. Part E. Preparation of Methyl 3- ( 4-N-Boc- amidinophenyl) isoxazolin-5-ylaceta ' te To a solution of 21.6 g (72.5 mmol) of methyl 3- (4- amidinophenyl) isoxazolin-5-ylacetate (prepared using the procedure of Example 434, Part D) in 350 ml DMF cooled with an ice bath was added 20.2 ml (145 mmol) of triethylamine and 17.4 g (79.8 mmol) of di-tert-butyl dicarbonate . The mixture was warmed to room temperature and stirred for 16 hours. The reaction mixture was poured into 1500 ml water while stirring. A while precipitate formed and was then filtered and dried on the filter under nitrogen to give 19.6 g (74.8%) of the title compound as a white solid. MS (ESI) : m/e 362 (M+H) + ; 306 (M+H-tBu) + . i H NMR (300 MHz, d 6 -DMSO) : 5 1.56 (s, 9H) ; 2.68 (dd, J = 6.1, 6.1 Hz, IH) ; 2.90 (dd, J = 6.1, 6.1 Hz, IH); 3.14 (dd, J = 6.8, 6.8 Hz, IH) ; 3.56 (dd, J = 6.8, 6.8 Hz, IH) ; 3.74 (s, 3H) ; 5.14 (m, IH) ; 7.70 (d, J = 8.4 Hz, 2H) ; 7.90 (d, J = 8.4 Hz, 2H) . 13 C NMR (60 MHz, d 6 -DMSO) : 528.46; 39.31; 39.58; 51.98; 77.89; 78.35; 126.91; 128.51; 132.79; 136.24; 156.86; 164.04; 165.76; 170.93. Part F. Preparation of 3- (4-N-Boc- amidinophenyl) isoxazolin-5ylacetic Acid To a solution of 18.95 g (52.4 mmol) of methyl 3- (4-N-Boc-amidinophenyl) isoxazolin-5-ylacetate (prepared using the procedure of Example 434, Part E) in 500 ml methanol was added 2.42 g (57.7 mmol) of lithium hydroxide monohydrate in 75 ml water at 22°C. The mixture was stirred at 22°C for 16 hours and then filtered; the filtrate was then evaporated under reduced pressure to remove methanol. The residual aqueous phase was cooled with an ice bath and acidified with 6 Ν and 1 N HCI to pH = 4. A white solid precipitated and it was left at -4°C overnight . The solid was filtered and dried on the filter under nitrogen to give 17.74 g (97.4%) of the title compound as an off-white powder. MS (ESI) : m/e 348 (M+H) + ; 292 (M+H-tBu) + . X H NMR (300 MHz, d 6 -DMSO) : 51.50 (s, 9H) ; 2.68 (d, J = 7.0 Hz, 2H) ; 3.22 (dd, J = 7.2, 7.2 Hz, IH) ; 3.62 (dd, J = 6.8, 7.2 Hz, IH) ; 5.04 (m, IH) ; 7.78 (d, J = 8.4 Hz, 2H) ; 7.94 (d, J = 8.4 Hz, 2H) . i3 C NMR (60 MHz, d 6 -DMSO) : 528.27; 39.30; 40.44; 78.39; 81.55; 126.87; 129.43; 132.78; 133.87; 156.76; 158.61; 165.58; 171.91. Part G. Preparation of (S)-N α - [3- (4-N-Boc- Amidinophenyl)-isoxazolin-5- (R,S) -ylacetyl]-β- (O-t- butyl)-α-aspart-N- (2-phenylethyl) amide To a suspension of (S)-β- (O-t-butyl)-α-aspart-N- (2- phenylethyl)amide (0.30 g, 1.0 mmol), 3-(4-N-Boc- amidinophenyl)-isoxazolin-5-ylacetic acid (0.35 g, 1.0 mmol), and TBTU (0.32 g, 1.0 mmol) in EtOAc (20 mL) , was added triethylamine (460 μL, 0.33 g, 1.0 mmol) . The reaction mixture was stirred at room temperature for 4.5 hr. It was diluted with EtOAc (20 mL) , washed with pH 4 buffer, water, 5% NaHCθ3 and sat. NaCl, dried over anhydrous MgS0 4 , filtered, and concentrated in vacuo to give 0.58 g of solid. The crude product was purified by flash chromatography (100% EtOAc), affording 0.51 g (81%); i H NMR (300 MHz, CDC1 3 ) δ 7.89 (t, J = 8.1 Hz, 2H) , 7.69 (m, 2H) , 7.25-7.3 (m, 3H) , 7.15-7.25 (m, 4H) , 7.04 (d, J = 8.4 Hz, IH) , 6.65-6.80 (dt, IH) , 5.10 (bm, IH) , 4.71 (bm, IH) , 3.4-3.7 (bm, 3H) , 3.1-3.3 (octet, IH) , 2.75-2.95 (m, 3H) , 2.5-2.65 (m, 3H) , 1.56 (s, 9H) , 1.44 (d, 9H) ; Mass Spectrum (ESI, e/z, relative abundance) 622, (M+H) + , 100 %. Example 435 Preparation of (S) -N&- r.3- (4-Amidinophenyl)-i soxazolin-5- (R.S)-γlar_e+yll-α-aspart-N- (2-phenylethyl) amide, trifluoroacetic acid salt A solution of (S)-N- [3- (4-N α -Boc-amidinophenyl) - isoxazolin-5-ylacetyl]-β-(O-t-butyl)-α-aspart-N- (2- phenylethyl)amide (160 mg, 0.26 mmol) in trifluoroacetic acid (10 mL) and DCM (10 mL) was stirred at room temperature for three days. The solution was concentrated in vacuo to give 150 mg of product; i H NMR (300 MHz, CDCI3) 5 9.40 (bs, 2H) , 9.26 (bs, 2H) , 8.33 (t, J = 8.6, IH) , 7.85-8.0 (m, IH) , 7.88 (s, 4H) , 7.3 (m, IH) , 7.28 (d, J = 7.1, 2H) , 7.20 (d, J = 7.1, 2H) , 5.07 (bm, IH) , 4.56 (bm, IH) , 3.5-3.6 (octet, IH) , 3.26 (bt, J = 7.0, 2H) , 3.2 (m, IH) , 2.70 (bt, J = 7.0, 2H) , 2.6-2.65 (bm, 2H) , 2.4-2.5 (m, 2H) ; Mass Spectrum (ESI, e/z, relative abundance) 466, (M+H) + , 100%. Examples 73A and 473B Resolution of Methyl N -3-methylphenylsulfonyl-N 3 -- T3-(4- amidinophenyl)-5S-ylacetyll-S-2.3-diaminopropionate trifluprpacetic and Methyl N2.-3-methylphenylsulfonγl- N 3 --T3-(4-amidinophenyl)-5R-γlacetyl1-S-2.3- diaminopropionate hydrochloride The mixture was initially purified on a Pirkle DNBPG column using 10%HOAc/20%EtOH/70% hexane as the eluting solvent. The column temperature was maintained at 45°C, the flow rate at 1.5ml/min, and the detector set at 280nm. The diastereomers were then separated on a chiralcel OD-25 X 2cm column using an eluting solvent of 0.1%TFA/20%MeOH/80%CO 2 . The column temperature was maintained at 30°C, the flow rate at 13ml/min, the pressure at 175 atm, and the detector was set at 280nm. Injections were made on 23mg of sample. Over the two columns a total of 300mg was injected giving 59mg of the R isomer, Ex. 473A (HRMS calc'd for C 2 3H 27 N5O6S 502.176031 Found: 502.175508) and 85mg of the S isomer, Ex. 473B (HRMS calc'd for C2 3 H 27 N 5 O6S 502.176031 Found: 502.176358) . Exaπφle 73C N2-3-methvlphenvlsulfonyl-N— T3- (4-amidinophenvl)-5S- ylacetyl1-S-2_ 3-diaminoprppipnic acid Part A: Methγl-N^-3-methylphenyl lfonyl-N 3 -- T3- (4- cyanophenvl)-5S-vlacetγl 1-S-2.3-diaminopropionate Into a solution of 3- (4-cyanophenyl) isoxazolin-5-S- ylacetic acid (1.82g, 7.90mmol, obtained as described in Es. 314A, part F) in DMF (50ml) was added methyl-N 2 -3- methylphenylsulfonyl-L-2,3-diaminopropionate HCI salt (2.77g, 7.90mmol), TBTU (2.53g, 7.90mmol), and Hϋnigs base (2.75ml, 15.8mmol) . After stirring at room temperature for 16 hours, the reaction mixture was diluted with EtOAc (500ml) and washed one time with water (200ml), one time with sat'd NaHCθ3 (200ml), one time with 0.IN HCI (200ml), dried (MgSθ 4 ) , filtered, and concentrated. Column chromatography on silica gel using 10% EtOAc/hexane as the eluting solvent gave 1.99g (52%) of the desired material as an off-white foam. X H NMR: (CDCI3) : δ 7.81-7.78 (d, 2H, J=8.4Hz); 7.16-7.67 (d, 2H, J=8.8Hz); 7.61-7.58 (m, 2H) ; 7.39-7.37 (d, 2H, J=5.1Hz); 6.35-6.30 (m, IH) ; 5.54-5.52 (d, IH, J=7.7Hz); 5.18-5.17 (m, IH) ; 4.00-3.96 (m, IH) ; 3.62-3.50 (m, 3H) ; 3.57 (s, 3H) ; 3.27-3.19 (dd, IH, J-7.7, 17.0Hz); 2.78- 2.70 (dd, IH, J=5.9, 14.8Hz) ; 2.64-2.57 (dd, IH, J=6.6, 14.6Hz) ; 2.42 (s, 3H) . Part B : Methyl-N^-3-methylphenyl su l f onyl -N3- r .3- ( 4- amidinopheny 1 ) -5S-ylacetyl 1 -S-2 . 3-diaminopropionate hydrpchlpride Methyl-N 2 -3-methylphenylsulfonyl-N 3 - [3- (4- cyanophenyl)-5S-ylacetyl]-S-2,3-diaminopropionate was dissolved in 100ml absolute ethanol at 0°c and a stream of HCI gas was bubbled through the solution for two hours. The reaction vessel was sealed and after sitting at room temperature for 16 hours the volatiles were removed in vacuo . The residue was then diluted with 100ml of absolute ethanol, ammonium carbonate (9.6g, 0.123mol) was added and after stirring for 16 hours the reaction mixture was filtered and concentrated in vacuo . Column chromatography on silica using a gradient elution from 5%MeOH/CH2Cl2 to 20%MeOH/CH2Cl2 gave 0.762g (37%) of the desired amidine as a white solid. i H NMR (CDCI3) : δ 8.23-8.20 (m, IH) ; 7.91-7.85 (m, 4H) ; 7.57-7.54 (m, 2H) ; 7.49-7.46 (m, 2H) ; 5.00-4.94 (m, IH) ; 4.08-3.86 (m, IH) ; 3.59-3.49 (m, IH) ; 3.39 (s, 3H) ; 3.38-3.29 (m, 3H) ; 2.49 (s, 3H) ; 2.50-2.45 (m, 2H) . HRMS: calc'd for C23H2 7 N5O6S 502.176031 found 502.175992. [α] D = +48.88° (c=0.180, MeOH) . Part C: N 2 -3-methylphenylsulfonyl-N 3 - [3- (4- amidinophenyl) 5 (S)-y1]acetyl-S-2,3-diaminopropionic acid The compound of Ex 473C, part B (0.077 g., 0.14 mmol) was dissolved in MeOH (4ml) . To the resulting solution was added a solution of lithium hydroxide (0.0066 g., 0.158 mmol) in water (4 ml) and the mixture was stirred overnight at room temperature. The methanol was removed by evaporation in vacuo, and the product precipitated from the aqueous as a white solid (0.026 g., 35%) . HRMS calcd for C 22 H 25 N 5 O6S: 488.160381; found: 488.160827. Example 473P Methyl-N^-3-methyl henylsuIfonyl-N 3 -- L3- 14- amidinopheny1 )-5R-yl cetyl1-S-2.3-diaminopropionate hydrochloride Part A: Methyl-N^-3-methylphenylsulfonyl-N 3 -- 3- 14- cyanophenyl)-5R-ylacetyl!-S-2.3-diaminopropionate This compound was synthesized from 3- (4- cyanophenyl) isoxazolin-5- (R)-ylacetic acid (3.07g, O.Ollmol, obtained as described in Ex. 314B, part B) using the same procedure as for example 473C, part A. Yield 41%. Theory: C 57.02, H 4.99, N 11.56 Found: C 56.83, H 4.87, N 11.45. Par B: Methyl-N^-S-methylphenylsulfonyl-N- f3- (4- amidinophenyl)-5R-ylacetyl 1-S-2. -rii aminopropionate hydrochloride This compound was synthesized from Methyl-N 2 -3- methylphenylsulfonyl-N 3 - [3- (4-cyanophenyl)-5R-ylacetyl]- S-2,3-diaminopropionate using the same procedure as for example 473C, part B. Yield 49%. HRMS Calc'd for C 2 3H2 7 N 5 O6S 502.176031 Found: 502.174103. Example 496 Methyl N 2 --(2,2-diphenyl-l-et.henef. lfonyl)-N 3 --f3-(4- amidinophenyl) isoxazol in-5- (R. )-ylacetyl1- (S)-2.3- diaminopropionate r trifluoroacetic acid salt Part A: Methyl N2- (2.2-di henyl-1-ethenesulfonyl)-N 3 -- Boc- (S)-2.3-diaminopropionat . To a mixture of methyl N 3 -Boc- (S)-2, 3- diaminopropionate (255 mg, 1.17 mmol) and 2,2- diphenylethylenesulfonyl chloride (Hasegawa and Hirooka, J. Chem. Soc. Japan 48,1513-1518 (1975); 391 mg, 1.40 mmol) in methylene chloride (10 mL) cooled in an ice bath was added triethylamine (0.25 mL, 1.76 mmol) . After 22 h, the mixture was concentrated and flash chromatographed (6:4 toluene/ethyl acetate) to provide 240 mg (46%) of product. NMR (CDC1 3 ) δ 7.42-7.20 (10H) , 6.81 (S,1H), 5.24 (bd, IH) , 4.87 (bs, IH) , 3.95 (q,lH), 3.72 (s,3H), 3.50-3.42 (2H) , 1.44 (s,9H); mass spec (NH3-CI) m/z 466.54 (M+NH4+, 100%) . Part B: Methyl N^- (2.2-diphenyl-1-ethenesul onyl )- (S)- 2.3-diaminopropionate TFA salt. The product of Part A (210 mg, 0.468 mmol) was dissolved in 5 mL of methylene chloride and 3 mL TFA. After 1 hour, the solution was concentrated to give an oily product. (222 mg, 100%) . NMR (DMSO-d6) δ 8.02 (bs, 3H),7.40 (m, 5H),7.23 (m, 4H) , 7.00 (s, IH) , 4.26 (m, IH) , 3.71 (s, 3H) , 3.20 (m, IH) , 2.98 (m, IH) . Part C: Methyl N 2 - (2.2-diphenyl-1-ethenesulfonyl)-N 3 -- T3- (4-N-Boo-amidi.nophenyl ) isoxazo! in-5- (R. S)-ylacetyl 1-(S)- 2. -diaminopropionate. The product of part B (220 mg, 0.46 mmol) was reacted with 3- (4-N-Boc-amidinophenyl)-isoxazolin-5- ylacetic acid (from Example 434 , part F; 160 mg, 0.46 mmol) , according to the procedure of example DGB-1, Part A, to provide the title product (215 mg, 68%) . NMR (CDCI3) δ 7.84 (m,2H), 7.64 (m,2H), 7.40-7.18 (10H) , 6.75 (s,lH), 6.30 (m,lH), 5.30 (m, IH) , 5.04 (m, IH) , 4.00 (IH), 3.78 (s,3H), 3.62-3.40 (4H) , 3.10 (m, IH) , 2.70- 2.50 (2H) , 2.04 (s,lH), 1.58 (s, 9H) ; mass spec (ESI) m/z 690.2 (M+H + , 100%) . Part D: Methyl N2- (2.2-diphenvl-1-ethenesulfonvl)-N 3 -- \3- (4-amidinophenvl) isoxazolin-5- (R.S) -ylacetvl!- (S)-2.3- diaminopropionate. trifluoroacetic acid salt The product of part C (210 mg, 0.30 mmol) was dissolved in methylene chloride (3 mL) and treated with trifluoroacetic acid (1 mL) according to the procedure of example DGB-1, Part B, to provide the title product (150 mg, 80%) . NMR (DMSO-d 6 ) δ 9.39 (bs,2H), 9.05 (bs,2H), 8.22 (m,lH), 8.00 (m, IH) , 7.85 (s,4H), 7.40 (m,6H), 7.20 (m, 4H) , 6.89 (s, IH) , 5.00 (m, IH) , 4.00 (m,IH), 3.70-3.18 (5H) , 3.62 (2s,3H); mass spec (ESI) m/z 590.2 (M+H+, 100%) Example 511. Methyl N2- (N.N-di ethvlsulfamovl)-N-- 13- (4- ami inophenyl ) i sox zolin-5- (R. ) -ylacetyl!- (S)-2.3- diaminopropionate f trifluoroacetic acid salt Fart A: Methyl N 2 -(N,N-dimethyl RulfamoyD-N^-Boc-(S)- 2.3-diaminopropionat . To a mixture of methyl N 3 -Boc- (S)-2, 3- diaminopropionate (400 mg, 1.80 mmol) and Dimethylsulfamoyl chloride (0.24 mL, 2.20 mmol) in methylene chloride (10 mL) cooled in an ice bath was added triethylamine (0.38 mL, 2.20 mmol) . After 18 h, the mixture was concentrated and flash chromatographed (6:4 toluene/ethyl acetate) to provide 283 mg (49%) of product. NMR (CDC1 3 ) δ 5.23 (bd, IH) , 4.90 (m, IH) , 4.06 (m,lH), 3.80 (s,3H), 3.52 (bt,2H), 2.80 (s,6H), 1.42 (s,9H); mass spec (NH3-CI) m/z 343.0 (M+NH 4 + , 100%) . Part R_ Methyl 2- (N.N-dimethvl sulfamoyl)- (S) -2.3- dia inopropionate TFA salt. The Product of Part A was dissolved in 5 mL of methylene chloride and 3 mL TFA. After 1 hour, the solution was concentrated to give an oily product (294 mg, 100%) . NMR (DMSO-dβ) δ 6.52 (bs,2H), 4.4-3.9 (2H) , 3.8 (bs,3H), 2.93 (bs,6H) . Part C_ Methyl 2- (N.N-ri methyl sulfamoyl)-N- 3 -- \3- (4-N- Boc-amidinophenyl) isoxazolin-5- (R f S) -ylacetyl!-L-2.3- diaminopropionate. The product of part B (200 mg, 0.61 mmol) was reacted with 3-(4-N-Boc-amidinophenyl) isoxazolin-5- ylacetic acid (from Example 434, part F; 212 mg, 0.61 mmol) , according to the procedure of DGB-1, Part A, to provide the title product (203 mg, 61%) . NMR (CDCI3) δ 7.78 (m,2H), 7.42 (bt,2H), 7.00 (m, IH) , 5.92 (m, IH) , 5.04 (m,lH), 3.80 (2s,3H), 3.64 (m,2H), 3.40 (m, IH) , 3.05 (m,lH), 2.80 (2s,6H), 2.74 (m, IH) , 2.60 (m, IH) , 2.02 (s,3H), 1.60 (s,9H); mass spec (ESI) m/z 555.1 (M+H+, 100%) . Part D: Methyl 2- (N.N-dimethyl sulfamoyl)-N 3 -- f3- 14- amidinophenvl ) isoxazol in-5- (R.S)-ylacetyl 1-L-2. - diaminopropionate. tr luoroace ic acid salt The product of part C (183 mg, 0.329 mmol) was dissolved in methylene chloride (3 mL) and treated with trifluoroacetic acid (1 mL) according to the procedure of example DGB-1, Part B, to provide the title product (159 mg, 85%) . NMR (DMSO-dβ) δ 9.40 (bs,2H), 9.00 (bs,2H), 8.22 (m,lH), 7.82 (s,4H), 5.00 (m, IH) , 3.95 (m,lH), 3.68 (2s,3H), 3.60 (m,2H) , 3.20 (m,4H), 2.80 (s,6H); mass spec (ESI) m/z 455.1 (M+H+, 100%) . Example 512 Methyl N 2 - (m-toluenesulfonyl)-N 3 -- T3- (4-amidino-2- fluorophenyl) isoxazolin-5-ylacetyl! -S-2. 3- diaminopropionate hydrochloric acid salt Part A: 3-Fluoro-4-methylbenzamide 3-Fluoro-4-methylbenzoic acid (10 g, 65 mmol) was boiled in thionyl chloride (100 mL) under a drying tube for 2.5 h. The excess SOCI2 was removed by distillation. The oily acid chloride product was diluted with CH 2 CI 2 (100 mL) and cooled in an ice bath. Cone. aq. NH3 (20 mL) was added dropwise, and stirring continued at 0 °C for 0.5 h. The CH 2 CI 2 was removed in vacuo, then the residue was diluted with EtOAc. The mixture was extracted with sat. aq. Na 2 C03 (2x) , H 2 O, and brine, dried (MgSθ 4 ) , and concentrated to yield 9.9 g of a pale yellow solid; mp 161-163 °C; IR(KBr) 3382, 1654 cm -1 ; Anal. Calc. for CβH 8 FNO: C, 62.74; H, 5.27; N, 9.15; F, 12.40. Found: C, 62.66; H, 5.17; N, 9.12; F, 12.28. Part B: 3-Fluoro-4-methylbenzonitrile A solution of trichloroacetyl chloride (7.3 mL, 65 mmol) in CH2CI 2 (20 mL) was added dropwise over 0.5 h to a solution/suspension of the Part A amide (9.0 g, 59 mmol) and Et3N (17 mL, 120 mmol) in CH 2 CI 2 (80 mL) at 0 °C. After 40 min, the mixture was concentrated in vacuo, then diluted with Et 2 θ. This solution was extracted with 1 M HCI, sat. aq. NaHCθ3, H 2 O, and brine, then dried (MgS0 4 ) , and concentrated to yield 7.8 g of a tan solid; mp 45-47 °C; IR(KBr) 2232 cm" 1 ; HRMS, e/z Calc. for (M+H) + : 135.0484. Found: 135.0482. Part C: 2-Fluorp-4-cyanpbenzylhrpmide N-Bromosuccinimide (9.6 g, 54 mmol) and the part B substrate (7.3 g, 54 mmol) were heated under reflux in CCI 4 (100 mL) under N 2 with irradiation with a high intensity visible lamp for 2 h. After cooling to ambient temp., the mixture was filtered through a Celite pad and concentrated in vacuo . The crude product was recrystallized from hot cyclohexane (4x) to yield 4.5 g of off-white needles; mp 75-77 °C; IR(KBr) 2236 cm "1 ; HRMS, e/z Calc. for (M+H) + : 213.9668. Found: 213.9660. Part D: 2-Fluoro-4-cyanobenzaldehyde The part C benzyl bromide (3.68 g, 17 mmol), trimethylamine N-oxide dihydrate (7.6 g, 68 mmol), CH2CI 2 (15 mL) , and DMSO (30 mL) were stirred at 0 °C for a few h, slowly warming to ambient T overnight. The mixture was diluted with water (30 mL) and brine (30 mL) , and extracted with Et2θ (4x) . The combined organics were washed with brine, dried (MgSθ 4 ) , and concentrated to yield 1.1 g of a yellow solid; IR(KBr) 2238, 1706 cm "1 ; HRMS, e/z Calc. for (M+H) + : 150.0355. Found: 150.0341. Part E: 2-Fluoro-4-cyanobenzaldoxime The part D aldehyde (1.1 g, 7.4 mmol), hydroxylamine hydrochloride (1.0 g, 15 mmol), K 2 CO3 (1.0 g, 7.4 mmol), water (1 mL) , and MeOH (10 mL) were heated under reflux for 2.25 h. After brief cooling, the mixture was diluted with water, and the insoluble product was collected by filtration, then rinsed with more water. Drying under high vacuum provided 0.94 g of a pale yellow amorphous solid; mp 179-182 °C; IR(KBr) 3256, 2236, 1556 cm "1 ; HRMS, e/z Calc. for (M+H) + : 165.0464. Found: 165.0455. Part F: Methyl 3- (4-cyano-2-fluorophenyl) isoxazolin-5- ylacetate The part E oxime was allowed to react with Clorox and methyl vinylacetate in the usual way to afford the isoxazoline as a yellow solid in 32% yield; mp 92-94 °C; IR(KBr) 2240, 1746 cm "1 ; HRMS, e/z Calc. for (M+H) + : 263.0832. Found: 263.0818. Anal. Calc. for C 1 3H 11 FN2O3: C, 59.54; H, 4.23; N, 10.68; F, 7.24. Found: C, 59.84; H, 4.31; N, 10.53; F, 7.26. Part G: Methyl N 2 - (m-toluenesulfonyl) -N-- f3- (4-amidino- 2-fluorophenyl) isoxazolin-5-ylacetyll-5-2.3- diaminopropionate hydrochloric acid salt The part F intermediate was converted to the title compound via the usual sequence of steps: Pinner amidine synthesis, amidine BOC protection, ester saponification, condensation with the 2,3- diaminopropionate sulfonamide ester, and BOC deprotection to provide a yellow gum; HRMS, e/z Calc. for (M+H) + : 520.1666. Found: 520.1675. Example 513 Methyl N 2 - (n-butyloxycarbonyl ) -N 3 -- T3- (3-amidinopyrid-6- yl ) isoxazolin-5-yl.acetyl 1 -S-7 .3-diaminopropionate bis hydrochloric acid salt Prepared using methods described in Ex. 514 to provide a pale yellow powder; mp 90-110 °C (dec) ; HRMS, e/z Calc. for (M+H) + : 449.2149. Found: 449.2140. Example 514 Methyl N 2 -- (m-toluenesulfonyl )-N 3 -- \3- (3-amidinopyrid-6- yl) isoxazolin-5-ylacetyl!-S-2 r 3-diaminopropionate bis hydrochloric acid salt Part A: 3-cyano-6-pyridaldoxime 5-Cyano-2-picoline (25 g, 0.21 mol) and I2 were heated under reflux in DMSO (200 mL) for 1 h. After cooling to RT, hydroxylamine hydrochloride (16 g, 0.23 mol), K2CO3 (29 g, 0.21 mol), and water (21 mL) were added. The resulting mixture was heated to 80 °C for 2.5 h, cooled, diluted with water (100 mL) and much acetone, and absorbed onto silica gel by concentration. Chromatography on silica gel, eluting with 0% to 50% EtOAc in hexane, afforded 12.2 g of a tan solid; mp 204-207 °C (dec); HRMS, e/z Calc. for (M+H) + : 148.0511. Found: 148.0516. Part B: Methvl 3- (3-cyanopyrid-6-vl) isoxazolin-5- ylacetate The oxime of Ex. 514, part A was converted to the isoxazoline as described in Ex. 516, part B in 76% yield as a yellow solid; mp 97-98 °C; HRMS, e/z Calc. for (M+H) + : 246.0879. Found: 246.0881. Anal. Calc. for C 1 2H 11 N3O3: C, 58.77; H, 4.52; N, 17.13. Found: C, 58.74; H, 4.51; N, 17.11. Part C: Methyl 3- (3-t-butyloxycarbonylamidinopyrid-6- yl) isoxazolin-5-ylacetate The nitrile of Ex. 514, part B was converted to the amidine as described in the method of Ex. 516, parts D & E (except that 0.6 eq. NaOMe was required), and BOC protected in standard fashion to afford, after purification, a yellow solid; mp 143 °C (gas evolves) ; HRMS, e/z Calc. for (M+H) + : 363.1668. Found: 363.1675. Anal. Calc. for C 17 H 22 N 4 O 5 : C, 56.35; H, 6.12; N, 15.46. Found: C, 56.35; H, 6.10; N, 15.39. Part D: Lithium 3- (3- -butyloxycarbonylamidinopyrid-6- yl) isoxazolin-5-ylacetate The ester of Ex. 514, part C was saponified and lyophilized as described in the method of Ex. 516, part F to give a colorless amorphous solid quantitatively; mp >230 °C; HRMS, e/z Calc. for conjugate acid (M+H) + : 349.1512. Found: 349.1527. Part E: Methyl N 2 - (m-toluenes lfonyl )-N-- T3- (3- amidinopyrid-6-yl) isoxazolin-5-ylacetyll -S-2 r 3- diaminopropionate bis hydrochloric acid salt The part D lithium carboxylate was converted to the title compound by treatment with HCI in MeOH to provide a yellow solid; mp 90 °C (dec); HRMS, e/z Calc. for (M+H) + : 503.1713. Found: 507.1718. Exa ple 515 Methyl N^- (n-butyloxycarbonyl ) -N 3 -- T3- (2-amidinopvrid-5- yl) isoxazolin-5-ylacetyl !-.9-2.3-diaminopropionate bis hydrochloric acid salt In similar fashion to the method described in Ex. 516, the compound of Ex. 514, part E was coupled with methyl N 2 - (n-butyloxycarbonyl)-2,3-diaminopropionate hydrochloride using conditions described above, followed by BOC deprotection with 4 M HCl/dioxane to yield a pale yellow powder; HRMS, e/z Calc. for (M+H) + : 449.2149. Found: 449.2154. Example 516 Methyl N2- (m-toluenesulfonyl ) -N 3 -- T3- (2-amidinopyrid-5- vl) isoxazolin-5-ylaoetyl 1 -S-2 .3-diaminopropionate bis hydrochloric acid salt Part A: 2-Chloro-5-pyridaldoxime 2-Chloro-5-formylpyridine (2.1 g, 15 mmol) was condensed with hydroxylamine hydrochloride in the usual way to give the oxime, 1.5 g, as a yellow crystalline solid; mp 171-175 °C (dec); HRMS, e/z Calc. for (M+H) + : 157.0169. Found: 157.0175. Part B: Methyl 3- (2-ohloropyri -5-yl ) isoxazolin-5- ylacetate Clorox (20 mL) was added dropwise over 1.75 h to a mixture of the part A oxime (1.13 g, 7.2 mmol), methyl vinylacetate (70% purity, 3.0 g, 21 mmol), CH2CI2 (40 mL) , and DMF (4 mL) with stirring at ambient temperature. The CH2CI 2 was evaporated, and the mixture was diluted with EtOAc, extracted with water (5x) and brine, then dried (MgSθ 4 ) , filtered, and concentrated. Chromatography on silica gel, eluting with 0% to 70% EtOAc in hexane, afforded 1.4 g of ' a solid; mp 94-96 °C; HRMS, e/z Calc. for (M+H) + : 255.0536. Found: 255.0531. Part C: Methyl 3- (2-cyanopyrid-5-yl) isoxazolin-5- ylacetate The part B chloropyridine (0.51 g, 2.0 mmol), zinc cyanide (0.23 g, 2.0 mmol), Pd(PPh3) (0.12 g, 0.10 mmol) , and DMF (2 mL) were heated to 80 °C under N 2 for 3 days. After cooling and concentration, the mixture was preabsorbed onto silica gel by concentration from CHCI 3 . Chromatography on silica gel, eluting with 0% to 90% EtOAc in hexane afforded 0.28 g of a pale yellow solid; mp 115-116 °C; HRMS, e/z Calc. for (M+H) + : 246.0879. Found: 246.0880. Anal. Calc. for C 12 H 11 N3O3: C, 58.77; H, 4.52; N, 17.13. Found: C, 58.68; H, 4.48; N, 16.90. Part D: Methyl 3- (2-amidinopyrid-5-yl) isoxazolin-5- ylacetate formic acid salt The part C cyanopyridine (0.47 g, 1.9 mmol) and sodium methoxide (prepared in situ from Na metal, 4 mg, 0.2 mmol were stirred in dry MeOH (6 mL) at ambient temperature for 16 h, after which i H NMR analysis of a reaction aliquot indicated complete formation of methyl imidate [note 9.25 (s, IH) and 3.92 (s, 3H) ] . Ammonium formate (0.60 g, 9.5 mmol) was added to the reaction mixture, and stirring continued for 7 h. The mixture was absorbed onto silica gel by concentration in vacuo . Chromatography on silica gel, eluting with 0% to 20% MeOH in CHCI3, and concentration afforded 0.61 g of the amidine as an off-white solid; mp 180-182 °C (dec) ; HRMS, e/z Calc. for (M+H) + : 263.1144. Found: 263.1148. Part E: Methvl 3- (2-t-butyloxycarbonylamidinopvrid-5- yl) isoxazplir.-5-ylacetate The part D amidine was BOC protected in standard fashion to afford, after silica gel chromatographic purification, a 41% yield of a colorless foam; HRMS, e/z Calc. for (M+H) + : 363.1668. Found: 363.1682. Part F: Lithium 3- (2- -hutyloxycarbonylamidinopvrid-5- yl) isoxazplin-5-ylacetat.e The part E methyl ester (0.37 g, 1.0 mmol) was saponified by stirring with 0.5 M LiOH in MeOH at RT. The MeOH was removed in vacuo, then the aqueous mixture was frozen and lyophilized to produce a pale yellow solid quantitatively; HRMS, e/z Calc. for conjugate acid (M+H) + : 349.1512. Found: 349.1531. Part G: Methyl N 2 - (m-toluenesulfonyl) -N 3 -- T3- (2- amidinopvrid-5-vl) isoxazolin-5-ylacetyll -S-2. 3- diaminopropionate bis hydrochloric acid salt The part F lithium carboxylate was condensed with methyl N 2 - (m-toluenesulfonyl)-2, 3-diaminopropionate hydrochloride using conditions described above, followed by standard BOC deprotection with 4 M HCl/dioxane to yield a yellow amorphous solid; HRMS, e/z Calc. for (M+H) + : 503.1713. Found: 503.1707. Example 548 Preparation of 3-bromothiophene-2-sulfonyl chloride A solution of chlorosulfonic acid (14.3 g, 0.12 mol) in 35 mL of 1, 2-dichloroethane was chilled to -10°C and protected from moisture, . Phosphorus pentachloride (20.8 g, 0.1 mol) was added in small portions while maintaining the temperature between -5° and -10°C. The resulting slurry was stirred at -10°C for 30 minutes. Then, 3-bromothiophene (16.3 g, 0.1 mol) was added dropwise over a period of 45 minutes, maintaining the temperature between -5° and +5°C. During the addition of the 3-bromothiophene, hydrogen chloride gas was evolved; the reaction mixture became thick and pasty, and difficult to stir. Upon complete addition of the 3- bromothiophene, the reaction temperature was held at 0°C for two hours. The reaction was then heated to 80°C and kept there for one hour; during which the solids dissolved, and hydrogen chloride gas was evolved once more . The reaction mixture was chilled in an ice bath, poured over 250 g crushed ice, and stirred for one hour as the ice melted. The resulting two phase system was separated and the aqueous layer washed three times with 125 mL of chloroform. The combined organic phases were dried over anhydrous MgSθ 4 , filtered, and concentrated in vacuo to give 24.1 g (92%) of crude product as a dark amber oil; i H NMR (300 MHz, CDC1 3 ) δ 7.22 (d, J = 5.3, IH) , 7.73 (d, J = 5.3, IH) ; Mass Spectrum (CH 4 -DCI / GC- MS, e/z, relative abundance) 262.8, (M+H) + , 100%; 226.9, (M+H-HCD+, 89.7%. Example 587A N 2 -3-methylphenylsulfonyl-N 3 -- T3- (4-amidinophenyl)-5S- ylacetyl1-S-2 r 3-diaminopropionic acid The compound of Example 473C, Part B (0.077g, 0.14mmol) was dissolved in MeOH (4ml), LiOH (0.0066g, 0.158mmol) in H2O (4ml) was added and the reaction mixture left to stir overnight. After evaporation of methanol the product precipitated from the aqueous as a white solid (0.027g, 35% yield) . HRMS calc'd for C 22 H 25 N 5 O6S: 488.160381 found: 488.160827. Example 6Q2 guanidinophenyl) isoxazolin-5- (R.S)-ylacetyl1- (S)-2.3- diaminopropionate, trifluoroacetic acid salt Fart ; r -r (4-t-butvloxvcarbonylamino)phenyll- isoxazolin-5-yllacetic acid: This compound was prepared in 49% yield from 4-t-butyloxycarbonylaminobenzaldoxime and t-butyl vinyl acetate using the procedure described above for Ex. 275, Part A. i HNMR(CDCl3) δ 0.99 (t, 3H) , 1.35 (m, 2H), 1.50 (s, 9H) , 1.61 (m, 2H) , 2.60 (dd, J = 7.7 and 16.5 Hz, IH) 2.84 (dd, J = 5.9 & 16Hz, IH) , 3.06 (dd, J = 7.4 & 16.9 Hz, IH) , 3.48 (dd, J = 10.3 & 16.5Hz, IH) , 4.10 (t, 2H) , 5.03 (m, IH) , 6.60 (broad s , IH) , 7.38 (d, J = 8.4 Hz, 2H) , 7.58 (J = 8.3Hz, 2H) ; IR(KBr) : 2966, 1734, 1740, 1610, 1578, 1528, 1508, 1458, 1442, 1412, 1392, 1368 1234, 1160, 1058, 916, 878, 828, 772, 612 cm "1 ; HRMS calcd. for C 20 H 2 8N 2 O5: 377.207647, Found 377.207278. Standard LiOH saponification conditions then afforded the corresponding carboxylic acid compound as colorless crystals in 88% yield, mp 178-180°C; i HNMR(CDCl3) δ 1.52 (s, 9H) , 2.67 (dd, J = 7.8 and 16 Hz, IH) , 2.89 (dd, J = 8.3 & 16Hz, IH) , 3.06 (dd, J = 9.5 & 16.9 Hz, IH) , 3.48 (dd, J = 10.3 & 16.5z, IH) , 5.03 (m, IH) . Part B: Methyl N^-n-hu+yloxycarhonyl-N 3 — L3- T (4-t- butvloxvcarbonvlamino)phenyl 1 i soxazolin-5-yl acetvl1- (S)-2 ,3-diaminopropionate: The compound of Example 602, Part A was condensed with methyl N -tBoc- (S)-2, 3- diaminopropionate using the procedure described for Ex. 275, Part C above to provide the desired product, mp 80-82°C; i HNMR(CDCl3) δ 1.88 (t,3H), 1.30 (m, 2H) , 1.47 (sm,20H), 2.50 (dd, IH) , 2.61 (dd, IH) , 3.07 (dd, IH) , 3.40 (dd,lH), 3.63 (t,2H), 3.74 (s,3H), 4.00 (m,2H), 4.38 (m,lH), 5.00 (m,lH), 5.88 (dd, IH) , 6.77 (t,lH), 7.58 (d,2H), 7.84 (d,2H), 10.4 (s, IH) , 11.6 (s, IH) ; IR(KBr) :3286, 2964, 1722, 1646, 1546, 1414, 1368, 1340, 1312, 1294, 1240, 1156, 1122, 1100, 1058, 1030, 844, 776 cm" 1 . Mass spectrum (CI/NH 4 ) 663 (M+H,20) , 563 (7) , 549(78), 506(81),463(100) . Part C: Methyl N^-n-butyloxycarbonyl-N 3 — (3- (4- quanidinophenyl) isoxazolin-5-yl acetyl!- (S)-2.3- diaminopropionate: The compound of Ex 602, part B was treated with TFA in dichloromethane to afford the corresponding aniline as its TFA salt. This intermediate was converted to the corresponding bis-BOC protected quanidino compound in 59% yield using the method of Kim et al. (Tet. Lett. 1993, 2, 7677) . Deprotection under standard conditions (TFA/CH 2 CI 2 ) provided the title compound as its TFA salt (90%) . i HNMR(DMSO-d6) δ 1.89 (t,3H), 1.34 (m, 2H) , 1.57 (m,2H), 2.44 (dd,lH), 2.58 (t,2H), 2.64 (m, IH) , 3.17 (m, IH) , 3.40 (m,2H), 3.65 (m,lH), 3.70 (s,3H), 4.00 (t,2H), 4.31 (m, IH), 5.02 (m,lH), 6.80 (m, IH) , 7.28 (d,2H), 7.64 (broads,3H) , 7.68 (d,2H), 7.84 (broad, IH) ; Mass spectrum(ES) m/z 463 (M+H, 100) . Example 651 Methyl ^-benzyloxycarbonyl-N 3 --methγl-N 3 — 13- (4- amidinophenyl) isoxazolin-5- (R r S)-ylacetyl1- (S) -2 , 3- diaminopropionate r trifluoroacetic acid salt Fart A. Preparation of methyl N2.-benzyloxycarbony1-N 3 -- methyl- r3- (4-N-Boc-amidinophenyl) isoxazolin-5- (R.S)- ylacetyl!- (S)-2.3-diaminopropionate. To a mixture of 3- (4-N-Boc-amidinophenyl)- isoxazolin-5-ylacetic acid (prepared according to the procedure of Example 434, part F; 189 mg, 0.54 mmol), methyl N 3 -methyl-N 2 -Cbz-L-2,3-diaminopropionate (prepared according to Sakai and Ohfune, J. Am. Chem. Soc. 114, 998 (1992); 145 mg, 0.54 mmol) and TBTU (175 mg, 0.54 mmol) in ethyl acetate (10 mL) was added triethylamine (0.15 mL, 1.09 mmol) . After stirring for 26 h, the mixture was diluted with ethyl acetate, washed with pH 4 buffer, then with saturated aqueous sodium bicarbonate, then with saturated brine. The organic phase was dried (MgS0 4 ) and concentrated. The residue was flash chromatographed (ethyl acetate) to provide the product as a colorless glass (279 mg, 86%) : NMR (CDCI3) δ 7.88 (m, 2H), 7.69 (m, 2H) , 5.79 (bd, IH) , 5.09 (m, 3H) , 4.58 (m, IH) , 3.86 (m, IH) , 3.77 (2s, 3H) , 3.63 (m, 2H) , 3.14 (dd, IH) , 3.01 (2s, 3H) , 2.9 (m, IH) , 2.53 (m, IH) , 1.66 (b, 2H) , 1.56 (s, 9H) ; mass spec (ESI) m/z 596.2 (M+H+, 100%) . Fart B. Preparation of Methyl N^benzyloxycarbonyl-N- 3 -- methyl-N 3 -- f3- (4-amidinophenyl ) isoxazolin-5- (R. S)- ylacetyl!-(S)-2.3-diam nopropionate, trifluoroacetic acid sal The product of part A (226 mg, 0.38 mmol) was dissolved in dichloromethane (3 mL) and treated with trifluoroacetic acid (1 mL) . After stirring at room temperature for 4 h, the mixture was diluted with ether and stirred. The resulting white solid was collected by filtration to provide the title product as a white solid (201 mg, 87%) : NMR (DMSO-dδ) δ 9.39 (bs, 2H) , 9.19 (bs, 2H), 7.87 (s, 4H) , 7.79 (t, IH) , 7.32 (m, 5H) , 5.03 (3H) , 4.40 (m, 2H) , 3.90 (m, IH) , 3.65 (2s, 3H) , 2.95 and 2.82 (4s, 3H) , 3.6-2.8 (4H) ; mass spec (ESI) m/z 496.3 (M+H+, 100%) . Example 7Q1 Methyl N^n-butyloxvcarbonvl-N 3 -- \3- (4- amidinophenyl) i ox o!-5-vl acetyl 1-L-2.3- diaminopropionate TFA salt . Part A. Preparation of Methyl 3- (4-cyanophenyl) isoxazo- 5-yl acetate To a suspension of methyl 3- (4-cyanophenyl)- (5R,S)- isoxazolin-5-yl acetate (5.28 g, 21.62 mmol) in chloroform (150 mL) were added N-bromosuccinimide (4.23 g, 23.78 mmol) and AIBΝ (100 mg) and the mixture was refluxed. Small amounts of AIBΝ (100 mg - 200 mg) were added at one hour intervals until TLC showed a complete reaction. Potassium acetate (17.3 g) and acetic acid (6.5 mL) were added and the reaction mixture was refluxed for 1 hour, cooled, then poured into IN ΝaOH (325 mL) . The organic layer was separated and the aqueous layer was extracted with EtOAc (3 x 100 mL) . The organic layers were combined and washed with sat. ΝaCl, dried over Νa2S0 4 , filtered, and concentrated in vacuo. The residue was chromatographed on silica gel (15% to 35% EtOAc in Hexane) to yield 2.2 g (42%) of an off-white solid as product; i H NMR (300 MHz, CDCI3) δ 7.93 (dd, 2H), 7.76 (dd, 2H) , 6.67 (s, IH) , 3.92 (s, 2H) , 3.8 (s, 3H) . Part B. Preparation of Methyl 3- (4- methoxyiminophenyl) isoxazo-5-yl acetate HC salt. A suspension of methyl 3-(4-cyanophenyl) isoxazo-5- yl acetate (2.19 g, 9.04 mmol) in 100 mL of anhydrous methanol was chilled in an ice bath and dry HCI gas was bubbled through the reaction mixture until a solution was obtained. The total addition time was two hours. The reaction flask was sealed and the reaction mixture was allowed to warm to room temperature, with stirring, over a period of about 24 hrs. At this point, the methanolic solution was poured into 500 mL of anhydrous ether, precipitating the product, and the resulting slurry was chilled to -25°C for 3 hours. The precipitate was filtered, washed with two 100 mL portions of chilled anhydrous ether, and suction dried under nitrogen to afford 2.3 g (82%) of the hydrochloride salt; i H NMR (300 MHz, suspension in CDCI3) δ 8.52 (d, J = 8.06 Hz, 2H) , 8.03 (d, J = 8.4 Hz, 2H) , 6 . 67 ( s , IH) , 4 . 6 ( s , 3H) , 3 . 93 ( s , 2H) , 3 . 8 ( s , 3H) . Fart C. Preparation of Methyl 3-(4- amidinophenyl) isoxazo-5-yl acetate HCI salt. A solution of methyl 3- (4- methoxyiminophenyl) isoxazo-5-yl acetate HCI salt (2.3 g, 7.4 mmol) in 50 mL of anhydrous methanol was chilled in an ice bath and 2M ammonia in methanol (18.5 mL, 37 mmol) was added. The reaction flask was sealed and the reaction mixture was allowed to warm to room temperature, with stirring, over a period of 24 hrs. The amber solution was then concentrated in vacuo to give 2.2 g (quant, yield) of a yellow foam; i H NMR (300 MHz, d6~DMSO) δ 9.6-9.2 (b) , 8.12 (d, J = 8.4 Hz, 2H) , 7.97 (d, J = 8.4 Hz, 2H) , 7.14 (s, IH) , 4.15 (s, 2H) , 3.7 (s, 3H) . Far D. Preparation of Methyl 3- ( 4-N-Boc- amidinpphenyl) ispχazp-5-yl acetate. To a solution of methyl 3- (4-amidinophenyl) isoxazo- 5-yl acetate HCI salt (2.2 g, 7.4 mmol) in 30 mL DMF cooled with an ice bath was added triethylamine (2.06 mL, 14.8 mmol) and di-tert-butyl dicarbonate (1.78 g, 8.14 mmol) . The reaction mixture was warmed to room temperature and stirred for 64 hrs. The reaction mixture was then partitioned between EtOAc and water. The aqueous layer was washed with EtOAc. The organic layers were combined and washed with water, sat. NaCl, dried over Na2Sθ , filtered, and concentrated in vacuo . The residue was chromatographed on silica gel (15% to 25% EtOAc in Hexane) to afford 1.45 g (54%) of product; i H NMR (300 MHz, CDC1 3 ) δ 7.96 (d, J = 8.4 Hz, 2H) , 7.87 (d, J == 8.4 Hz, 2H) , 6.65 (s, IH) , 3.91 (s, 2H) , 3.8 (s, 3H) , 1.56 (s, 9H) . Fart E. Preparation pf 3- ( 4-N-Boc- a idinpphenyl)ispχazp-5-yl acetic acid. To a solution of methyl 3- (4-N-Boc- amidinophenyl) isoxazo-5-yl acetate (1.45 g, 4.03 mmol) in 30 mL of methanol was added a solution of lithium hydroxide monohydrate (0.195 g, 4.64 mmol) in water (5 mL) . The mixture was stirred at room temperature for 16 hours. The reaction mixture was then concentrated in vacuo and the residue was diluted with water and the resulting mixture was cooled using an ice bath. IN HCI was slowly added to a pH of 3 - 4 and the resulting acidic aqueous mixture was extracted repeatedly with EtOAc. The organic layers were combined and washed with sat. NaCl, dried over Na2S0 4 , filtered and concentrated in vacuo to yield 0.97 g (70%) of an off-white powdery solid as product; i H NMR (300 MHz, d 6 -DMS0) δ 8.07 (d, J = 8.79 Hz, 2H), 7.97 (d, J = 8.4 Hz, 2H) , 7.03 (s, IH) , 3.99 (s, 2H) , 1.45 (s, 9H) . Part F. Preparation of Methyl N 2 -n-butyloxycarbonyl-N 3 - [3- ( 4-N-Boc-amidinophenyl) isoxazo-5-yl acetyl]-L-2,3- diaminopropionate. To a solution of 3- (4-N-Boc-amidinophenyl) isoxazo- 5-yl acetic acid (0.262 g, 0.76 mmol), methyl N 2 - carboxy-n-butyl-L-2,3-diaminopropionate HCI salt (0.193 g, 0.76 mmol), and TBTU (0.256 g, 0.8 mmol) in DMF (15 mL) was added triethylamine (0.45 mL, 3.23 mmol) and the resulting reaction mixture was allowed to stir at room temperature for 16 hours. The reaction mixture was partitioned between EtOAc and water. The water layer was washed twice with EtOAc. The organic layers were combined and washed with water, pH 4 buffer, 5% NaHC03, and sat. NaCl, dried over Na 2 S0 4 , filtered, and evaporated in vacuo. The residue was chromatographed on silica gel (100% EtOAc) to yield 0.315 g (76%) of a slightly amber foam; i H NMR (300 MHz, CDC1 3 ) δ 7.93 (d, J = 8.42 Hz, 2H) , 7.83 (d, J = 8.42 Hz, 2H) , 6.6 (s, IH), 6.57 (bm, IH) , 5.66 (bm, IH) , 4.45 (bm, IH) , 4.05 (m, 2H) , 3.77 (s, 5H) , 3.7 (m, 2H) , 1.57 (s, 9H) , 1.56 (m, 2H) , 1.35 (m, 2H) , 0.9 (t, J = 7.32 Hz, 3H) . Part G. Preparation of Methyl N 2 -n-butyloxycarbonyl-N 3 - [3- (4-amidinophenyl) isoxazo-5-yl acetyl]-L-2, 3- diaminopropionate TFA salt. A solution of methyl N 2 -carboxy-r_-butyl-N 3 - [3- ( 4-N- Boc-amidinopheny1) isoxazo-5-yl acetyl]-L-2,3- diaminopropionate (0.215 g, 0.39 mmol) in 1:1 methylene chloride / trifluoroacetic acid (20 mL total) was stirred at room temperature for 16 hours. The reaction mixture was then concentrated in vacuo and the residue chromatographed on silica gel (10% to 30% methanol in chloroform) to yield 0.11 g (50%) of a white solid; i H ΝMR (300 MHz, dε-DMSO) δ 9.4 (bs, 2H) , 9.15 (bs, 2H) , 8.45 (t, IH), 8.11 (d, J = 8.42 Hz, 2H) , 7.94 (d, J = 8.42 Hz, 2H), 7.53 (d, J = 8.06 Hz, IH) , 7.01 (s, IH) , 4.21 (m, IH), 3.95 (t, 2H) , 3.81 (s, 2H) , 3.62 (s, 3H) , 3.55 (m, IH) , 3.34 (m, IH) , 1.5 (m, 2H) , 1.3 (m, 2H) , 0.87 (t, J = 7.32 Hz, 3H) . ; Mass Spectrum (ESI, e/z, relative abundance) 446.3, (M+H) + , 100%. Example 829 Methvl Ν -n-butvloxycarbonvl-N- 3 — r5- (4- formamidinophenyl) isoxazolin-3-yl acetyl!- (2S) -2 . 3- diaminopropionate Far h : t-Butyl r5-(4-cyanophenyl) isoxazolin-3- yllacetate; Cycloaddition of 4-cyanophenylethylene (MP&D chemical Co.) and tert-butylformyl oxime was carried out following the procedure of Gree et. al. (Bioorganic & Medicinal Chemistry letters 1994, 253) to provide the desired isoxazoline in 72% yield. i HNMR(CDCl 3 ) δ: 1.40 (s, 9H) , 3.00 (dd, J - 8.3 and 17Hz, IH) , 3.35 (dd(AB) J = 18 and 8.3 Hz, 2H),3.48 (m, IH) , 5.60 (dd, J = 9 and 4.5 Hz, IH) , 7.47 (d, J = 8Hz, 2H) , 7.65 (d, J = 8 Hz, 2H) ; IR 2235, 1718, 1610 cm" 1 . Mass spectrum m/z 287 (M+H, 100) . Fart B; r.5-(4-cyanophenyl ) isoxazo ' l i n-3-y! 1 acetic acid: Hydrolysis of the compound of Ex.829, Part A with excess TFA in dichloromethane afforded the acid in 90% yield. i HNMR (CDCI3) δ 3.00 (dd, J = 8 and 17.2 Hz, IH) , 3.55 (s, 2H), 3.59 (m, IH) , 5.66 (dd, J = 8 and 11Hz, IH), 7.45 (d, J = 8.4 Hz, 2H) , 7.66 (d, J = 8.0 Hz, 2H) ; IR(KBr) 3325, 2235, 1718, 1605 cm "1 ; Mass spectrum m/z 231 (M+H, 100) . Part C: Methyl T5- (4-Boc-amidinophenyl) isoxazolin-3-yll acetate: The compound of Ex. 829, Part B compound was then subjected to the standard Pinner reaction conditions described in Ex. 275, Part D to afford an amidino compound, which, without purification, was subjected to treatment with di-tert-butyldicarbonate in dioxane/water (9:1) and excess triethylamine to afford the desired compound in 28% yield. i HNMR(CDCI3) δ 1.54 (s,9H), 2.98 (dd, J = 8 and 17 HZ, IH) , 3.49 (s, 2H) , 3.53 (m, IH) , 3.71 (s, 3H) , 5.63 (dd, J = 8 & 11.4Hz, IH) , 7.38 (d, 8.2Hz, 2H) , 7.82 ( (d, 8.2Hz, 2H) ; Mass spectrum m/z 362 (M+H, 8), 306(18), 262(M+H-Boc, 100) . Far D; f5- (4-Boc-amidinophenyl) isoxazolin-3-yllacetic acid: Hydrolysis of the ester using standard LiOH conditions afforded the desired acid in 5% yield. i HNMR(CDCl3) δ 1.54 (s,9H), 3.00 (dd, J = 8 and 17 HZ, IH) , 3.51 (s, 2H) , 3.53 (m, IH) , 5.63 (dd, J = 8 & 11.4Hz, IH) , 7.38 (d, 8.2Hz, 2H) , 7.82 ( (d, 8.2Hz, 2H) ; Mass spectrum m/z 348 (M+H, 12) ,248 (M+H-Boc, 100) . Far E: Methvl N^n-butyloxycarbonyl-N 3 — r.S- (4-amidino phenyl) isoxazolin-3-yl-acetyl1 (S)-2 f 3-diaminopropionate. trifluoroacetat : The compound of Ex. 829, Part D was coupled with methyl- (S)-N2-n-butyloxycarbonyl-2,3- diaminopropionate following the procedure described in Ex. 275, Part C to give the Boc protected intermediate in 80% yield. iHNMR(CDCl3) δ 0.89 (t, 3H) , 1.32 (m, 2H) , 1.53 (s, 9H), 1.17 (m, 2H) , 2.95 (dd, J = 8 and 17 HZ, IH) , 3.33 (s, 2H) , 3.46 (m, IH) , 3.60 (m, 2H) , 3.73 (s, 3H) , 4.00 (m, 2H) , 4.31 (m, IH) , 5.60 (dd, J = 8 & 11.4Hz, IH) , 5.70 (bd, IH) , 6.70 (broad, IH) , 7.33 (d, 8.2Hz, 2H) , 7.89 ( (d, 8.2Hz, 2H) ; Mass spectrum m/z 534 (M+H, 30), 434 (M+H-Boc, 100) . Deprotection by treatment of the above Boc-amidine with excess TFA in dichloromethane provided the title compound as the TFA salt. i HNMR(CDCl3/DMSO-d6) δ 1.88 (t, 3H) , 1.30 ( , 2H) , 1.53 ( , 2H) , 3.00 (dd, J = 8 and 17 HZ, IH) , 3.32 (s, 2H) , 3.40-3.63 (m, 3H) , 3.63 (d, 3H) , 3.98 (t, 2H) , 4.29 (m, IH), 5.60 (dd, J = 8 & 11Hz, IH) , 6.80 (d, IH) , 7.50 (d, J = 8Hz, 2H) , 7.80 (d, J = 8.2Hz, 2H) , 8.03 (broad s, IH) , 9.05 (broad s, 2H) ; IR(KBr) : 3388, 1718, 1664, 1620, 1528, 1456, 1436, 1384, 1366, 1280, 1254, 1168, 1144, 1074, 980, 882, 778 cm" 1 ; Mass spectrum(ES) m/z 448 (M+H, 100) Using the above methods and variations thereof known in the art of organic synthesis, the additional examples in Tables 1-2, 2A-2D, 3-5 can be prepared. n R 14 n' n R" n R 8 Y MS (M+H) + Example R2 R β MS Number (M+H) + 97 H OMe 98 H OMe 101 H - J ~CN OMe 102 H ri OMe Example R 2 R 8 Y MS Number (M+H) + 467 H OMe 510 "" 468 H OMe 46: N i v_ 587 H - ( CH 2 ) 3 -(4-pyr) OH 424 Table 2ft 306 4-amidinophenyl Example »!-* .16 MS Number (M+H) ' 307 4-amidinophenyl 4-pyridylmethyl- OH carbonyl 308 4-amidinophenyl 2-pyridylmethoxy- OH carbonyl 309 4-amidinophenyl 3-pyridylmethoxy- OH carbonyl 310 4-amidinophenyl 4-pyridylmethoxy- OH carbonyl H benzyloxycarbonyl t-butyloxycarbonyl n-butyloxycarbonyl ethyloxycarbonyl methyloxycarbonyl phenylethylcarbonyl 2,2-dimethyl- propylcarbonyl n-pentylcarbonyl n-butylcarbonyl propionyl acetyl methylsulfonyl ethylsulfonyl n-butylsulfonyl phenylsulfonyl 4-methylpheny1- sulfonyl benzylsulfonyl 2-pyridylcarbonyl 3-pyridylcarbonyl 4-pyridylcarbonyl Example -< V > 16 MS Number (M+H) + 332 4-amidinophenyl 2-pyridylmethyl- OMe carbonyl 333 4-amidinophenyl 3-ρyridylmethyl- OMe carbonyl 334 4-amidinophenyl 4-pyridylmethyl- OMe carbonyl 335 4-amidinophenyl 2-pyridylmethoxy- OMe carbonyl 336 4-amidinophenyl 3-pyridylmethoxy- OMe carbonyl 337 4-amidinophenyl 4-pyridylmethoxy- OMe carbonyl benzylcarbonyl benzyloxycarbonyl n-butyloxycarbonyl 1-naphthylsulfonyl 2-naphthylsulfonyl styrylsulfonyl n-butyloxycarbonyl 4-butyloxyphenyl- sulfonyl 2-thienylsulfonyl 3-methylphenyl- sulfonyl 474 4-amidinophenyl 4-iodophenyl 475 -amidinophenyl 3-trifluoromethyl¬ phenylsulfonyl 476 4-amidinophenyl 3-chlorophenyl- OMe 522 sulfonyl 477 4-amidinophenyl 2-methoxycarbony1- OMe 546 phenylsulfonyl Example »!-* ■ V R 16 MS Number (M+H) " 478 -amidinophenyl 2,4,6-trimethyl- OMe 530 phenylsulfonyl 479 4-amidinophenyl 2-chlorophenyl- OMe 522 sulfonyl 480 4-amidinophenyl 2-trifluoromethyl¬ OMe 556 phenylsulfonyl 481 4-amidinophen l 4-trifluoromethyl¬ OMe 556 phenylsulfonyl 482 4-amidinophenyl 2-fluorophenyl¬ OMe 506 sulfonyl 483 4-amidinophenyl 4-fluorophenyl- OMe 506 sulfonyl 484 4-amidinophenyl 4-methoxyphenyl- OMe 518 sulfonyl 485 4-amidinophenyl 2,3,5,6-tetramethyl- OMe 544 phenylsulfonyl 486 4-amidinophenyl 4-cyanophenyl- OMe 513 sulfonyl 487 4-amidinophenyl 4-chlorophenyl- OMe 522 sulfonyl 488 4-amidinophenyl 4-ethylphenyl- OMe 516 sulfonyl 489 4-amidinophenyl 4-propylpheny1- OMe 530 sulfonyl 490 4-amidinophenyl n-propylsulfonyl OMe 454 491 4-amidinophenyl 2-phenylethyl- OMe 516 sulfonyl 492 4-amidinophenyl 4-isopropylphenyl- OMe 530 sulfonyl 493 4-amidinophenyl 3-phenylpropyl- OMe 530 sulfonyl 494 4-amidinophenyl 3-pyridylsulfonyl OMe 489 Example .1-x ,16 MS Number (M+H) ' 495 4-amidinophenyl 496 4-amidinophenyl 497 4-amidinophenyl 498 4-amidinophenyl 499 4-amidinophenyl 500 4-amidinophenyl 501 4-amidinophenyl 502 4-amidinophenyl 503 4-amidinophenyl 504 4-amidinophenyl 505 4-amidinophenyl 506 4-amidinophenyl 507 4-amidinophenyl 508 4-amidinophenyl 509 4-amidinophenyl 510 4-amidinophenyl 511 4-amidinophenyl 512 4-amidino-2-fluoro¬ phenyl 513 2-amidino-5-pyridyl Example »l- •< V »16 MS Number (M+H) ' 514 2-amidino-5-pyridyl 3-methylphenyl- OMe 503 sulfonyl 515 3-amidino-6-pyridyl n-butyloxycarbonyl 516 3-amidino-6-pyridyl 3-methylphenyl- sulfonyl 517 4-amidinophenyl phenylaminocarbonyl 518 4-amidinophenyl 4-fluorophenylamino- carbonyl 519 4-amidinophenyl 1-naphthylamino- OMe 517 carbonyl benzylaminocarbonyl n-butylaminocarbonyl 4-ethylpheny1- carbonyl biphenylcarbonyl 2-naphthylcarbonyl (2-chlorophenyl) methoxycarbonyl 526 4-amidinophenyl (2-chlorophenyl) OH 502 methoxycarbonyl 527 4-amidinophenyl (2-bromophenyl) OMe 562 methoxycarbonyl 528 4-amidinophenyl (2-bromophenyl) OH 548 methoxycarbonyl 529 4-amidinophenyl n-hexyloxycarbonyl 530 4-amidinophenyl n-hexyloxycarbonyl 531 4-amidinophenyl isobutyloxycarbonyl 532 4-amidinophenyl isobutyloxycarbonyl 533 4-amidinophenyl 2-cyclopropylethoxy- carbonyl 534 4-amidinophenyl 2-cycloρropylethoxy- OH 446 carbonyl Example »1- •V »16 MS Number (M+H) ' 535 4-amidinophenyl 536 4-amidinophenyl 537 4-amidinophenyl 538 4-amidinophenyl 539 4-amidinophenyl 540 4-amidinophenyl 541 4-amidinophenyl 542 4-amidinophenyl 543 4-amidinophenyl 544 4-amidinophenyl 545 4-amidinophenyl 546 4-amidinophenyl 547 4-amidinophenyl 548 -amidinophenyl 549 4-amidinophenyl 550 4-amidinophenyl Example -V .16 MS Number (M+H) ' 551 4-amidinophenyl 5-(3-isoxazolyl)-2- OMe 561 thienylsulfonyl 552 4-amidinophenyl 5-(2-pyridinyl)-2- OMe 571 thienylsulfonyl 553 4-amidinophenyl 4-methyl-2- OMe 566 methylcarbonylamino-5- thiazolylsulfonyl 554 4-amidinophenyl 2-benzothienyl- OMe 628 sulfonyl 555 4-amidinophenyl 2-benzothienyl- OMe 544 sulfonyl 556 4-amidinophenyl 3-methyl-2- OMe 558 benzothienylsulfonyl 557 4-amidinophenyl 8-quinolinylsulfonyl OMe 558 4-amidinophenyl 8-quinolinylsulfonyl OH 559 -amidinophenyl 2,1,3-benzo- OMe thiadiazol-4-ylsulfonyl 560 4-amidinophenyl 2,1,3-benzo- OH thiadiazol-4-ylsulfonyl 561 4-amidinophenyl 4-N,N-dimethylamino-l- OMe naphthylsulfonyl 562 4-amidinophenyl 4-N,N-dimethylamino-l- OH haphthylsulfonyl 563 4-amidinophenyl 2,1,3-benzoxadiazol-4- OMe ylsulfonyl 564 4-amidinophenyl 2,1,3-benzoxadiazol-4- OH ylsulfonyl 565 4-amidinophenyl 2,2,5,7,8-pentamethyl OMe 3,4-dihydro-2Hbenzo- pyran-6-ylsulfonyl Example »l_t .16 Y MS Number (M+H) ' 566 4-amidinophenyl 2,2,5, 7, 8-pentamethyl OH 3,4-dihydro-2Hbenzo- pyran-6-ylsulfonyl 567 4-N-methylamidino 3-methylphenylsulfonyl OMe phenyl 568 4-N-ethylamidino 3-methylphenylsulfonyl OMe 530 phenyl 569 4-N-n-propylamidino 3-methylphenylsulfonyl OMe phenyl 570 -N-benzylamidino phenyl3-methylphenylsulfonyl OMe 571 4-N-n-butylamidino 3-methylphenylsulfonyl OMe phenyl 572 4-N-methylamidino 3-methylphenylsulfonyl OH phenyl 573 4-N-et ylamidino 3-methylphenylsulfonyl OH phenyl 574 -N-n-propylamidino 3-methylphenylsulfonyl OH phenyl 575 4-N-benzylamidino 3-methylphenylsulfonyl OH phenyl 576 4-N-n-butylamidino 3-methylphenylsulfonyl OH phenyl 577 4-N-methylamidino- n-butyloxycarbonyl OMe phenyl 578 4-N-ethylamidinophenyl n-butyloxycarbonyl OMe 579 4-N-nρropylamidino- n-butyloxycarbonyl OMe phenyl 580 4-N-n-butylamidino- n-butyloxycarbonyl OMe 504 phenyl 581 4-N-benzylamidino- n-butyloxycarbonyl OMe phenyl Example »l- •< V .16 MS Number (M+H) 582 4-N-methylamidino- n-butyloxycarbonyl OH phenyl 583 4-N-ethylamidino- n-butyloxycarbonyl OH phenyl 584 4-N-n-propylamidino- n-butyloxycarbonyl OH phenyl 585 4-N-n-butylamidino- n-butyloxycarbonyl OH phenyl 586 4-N-benzylamidino- n-butyloxycarbonyl OH phenyl 589 4-(acetoxyamidino)- n-butyloxycarbonyl OMe phenyl 590 4-(acetoxyamidino)- n-butyloxycarbonyl OH phenyl 591 4-(acetoxyamidino)- isobutyloxycarbonyl OMe phenyl 592 4-(acetoxyamidino)- isobutyloxycarbonyl OH phenyl 593 4-(acetoxyamidino)- cyclopropylethoxy- OMe phenyl carbonyl 594 4-(acetoxyamidino)- cyclopropylethoxy- OH phenyl carbonyl 595 4-(acetoxyamidino)- benzyloxycarbonyl OMe phenyl 596 4-(acetoxyamidino)- benzyloxycarbonyl OH phenyl 597 4-(acetoxyamidino)- 4-methylphenylsulfonyl OMe phenyl 598 4-(acetoxyamidino)- 4-methylphenylsulfonyl OH phenyl carbonyl 623 4-amidinophenylmethyl cyclopropylethoxy OH carbonyl 624 4-amidinophenylmethyl 4-methylphenylsulfonyl OMe 625 4-amidinophenylmethyl 4-methylphenylsulfonyl OH 626 4-amidinophenylmethyl 3-methylphenylsulfonyl OMe 627 4-amidinophenylmethyl 3-methylphenylsulfonyl OH Example R^—V .16 MS Number (M+H) ' 628 4-amidinophenylmethyl n-butylsulfonyl OMe 629 -amidinophenylmethyl n-butylsulfonyl OH 630 4-amidinophenylmethoxy benzyloxycarbonyl OMe 631 4-amidinophenylmethoxy benzyloxycarbonyl OH 632 4-amidinophenylmethoxy n-butyloxycarbonyl OMe 633 4-amidinophenylmethoxy n-butyloxycarbonyl OH 634 4-amidinophenylmethoxy cyclopropylethoxy OMe carbonyl 635 4-amidinophenylmethoxy cyclopropylethoxy OH carbonyl 636 4-amidinophenylmethoxy 4-methylphenylsulfonyl OMe 637 4-amidinophenylmethoxy 4-methylphenylsulfonyl OH 638 4-amidinophenylmethoxy 3-methylphenylsulfonyl OMe 639 4-amidinophenylmethoxy 3-methylphenylsulfonyl OH 640 4-amidinophenylmethoxy n-butylsulfonyl OMe 641 4-amidinophenylmethoxy n-butylsulfonyl OH 801 4-amidinophenoxymethyl benzyloxycarbonyl OMe 802 4-amidinophenoxymethyl benzyloxycarbonyl OH 803 4-amidinophenoxymethyl n-butyloxycarbonyl OMe 804 4-amidinophenoxymethyl n-butyloxycarbonyl OH 805 4-amidinophenoxymethyl cyclopropylethoxy OMe carbonyl 806 4-amidinophenoxymethyl cyclopropylethoxy OH carbonyl 807 4-amidinophenoxymethyl 4-methylphenylsulfonyl OMe 808 4-amidinophenoxymethyl 4-methylphenylsulfonyl OH 809 4-amidinophenoxymethyl 3-methylphenylsulfonyl OMe 810 4-amidinophenoxymethyl 3-methylphenylsulfonyl OH 811 4-amidinophenoxymethyl n-butylsulfonyl OMe 812 4-amidinophenoxymethyl n-butylsulfonyl OH 813 4-amidinophenoxy benzyloxycarbonyl OMe 814 4-amidinophenoxy benzyloxycarbonyl OH .16 MS (M+H) n-butyloxycarbonyl OMe n-butyloxycarbonyl OH cyclopropylethyoxy OHe carbonyl 819 4-amidinophenoxy cyclopropylethoxy OH carbonyl 820 4-amidinophenoxy 4-methylphenylsulfonyl OMe 821 4-amidinophenoxy 4-methylphenylsulfonyl OH 822 4-amidinophenoxy 3-methylphenylsulfonyl OMe 823 4-amidinophenoxy 3-methylphenylsulfonyl OH 824 4-amidinophenoxy n-butylsulfonyl OMe 825 4-amidinophenoxy n-butylsulfonyl OH 826 4-amidinophenethyl benzyloxycarbonyl OMe 827 4-amidinophenethyl benzyloxycarbonyl OH 828 4-amidinophenethyl n-butyloxycarbonyl OMe 829 4-amidinophenethyl n-butyloxycarbonyl OH 830 4-amidinophenethyl cyclopropylethoxy OMe carbonyl 831 4-amidinophenethyl cyclopropylethoxy OH carbonyl 832 4-amidinophenethyl 4-methylphenylsulfonyl OMe 833 4-amidinophenethyl 4-methylphenylsulfonyl OH 834 4-amidinophenethyl 3-methylphenylsulfonyl OMe 835 4-amidinophenethyl 3-methylphenylsulfonyl OH 836 4-amidinophenethyl n-butylsulfonyl OMe 837 4-amidinophenethyl n-butylsulfonyl OH 838 N-(4-amidinophenyl) benzyloxycarbonyl OMe aminomethyl 839 N-(4-amidinophenyl) benzyloxycarbonyl OH aminomethyl R 16 MS (M+H) ' n-butyloxycarbonyl OMe n-butyloxycarbonyl OH cyclopropylethoxy OH carbonyl 4-methylphenylsulfonyl OMe 4-methylphenylsulfonyl OH 3-methylphenylsulfonyl OMe 3-methylphenylsulfonyl OH n-butylsulfonyl OMe n-butylsulfonyl OH benzyloxycarbonyl OMe benzyloxycarbonyl OH n-butyloxycarbonyl OMe n-butyloxycarbonyl OH cyclopropylethoxy OMe carbonyl cyclopropylethoxy OH carbonyl 4-methylphenylsulfonyl OMe R 16 MS (M+H) 4-methylphenylsulfonyl OH 3-methylphenylsulfonyl OMe n-butylsulfonyl OMe n-butylsulfonyl OH benzyloxycarbonyl OMe benzyloxycarbonyl OH n-butyloxycarbonyl OMe n-butyloxycarbonyl OH cyclopropylethoxy OMe carbonyl cyclopropylethoxy OH carbonyl 4-methylphenylsulfonyl OMe 4-methylphenylsulfonyl OH 3-methylphenylsulfonyl OMe 3-methylphenylsulfonyl OH n-butylsulfonyl OMe n-butylsulfonyl OH Example »l_ι ,16 MS Number (M+H) ' 872 -amidinophenyl benzyloxycarbonyl OMe carbonylamino 873 -amidinophenyl benzyloxycarbonyl OH carbonylamino 874 4-amidinophenyl n-butyloxycarbonyl OMe carbonylamino 875 4-amidinophenyl n-butyloxycarbonyl OH carbonylamino 876 4-amidinophenyl cyclopropylethoxy OMe carbonylamino carbonyl 877 4-amidinophenyl cyclopropylethoxy OH carbonylamino carbonyl 878 4-amidinophenyl 4-methylphenylsulfonyl OMe carbonylamino 879 4-amidinophenyl 4-methylphenylsulfonyl OH carbonylamino 880 4-amidinophenyl 3-methylρhenylsulfonyl OMe carbonylamino 881 4-amidinophenyl 3-methylphenylsulfonyl OH carbonylamino 882 4-amidinophenyl n-butylsulfonyl OMe carbonylamino 883 4-amidinophenyl n-butylsulfonyl OH carbonylamino 884 N-(4-amidinophenyl) benzyloxycarbonyl OMe amino 885 N-(4-amidinophenyl) benzyloxycarbonyl OH amino 886 N-(4-amidinophenyl) n-butyloxycarbonyl OMe amino 887 N-(4-amidinophenyl) n-butyloxycarbonyl OH ammo Example R 1 -V »16 MS Number (M+H) ' 888 N-(4-amidinophenyl) cyclopropylethoxy OMe amino carbonyl 889 N-(4-amidinophenyl) cyclopropylethoxy OH amino carbonyl 890 N-(4-amidinophenyl) 4-methylphenylsulfonyl OMe amino 891 N-(4-amidinophenyl) 4-methylphenylsulfonyl OH amino 892 N-(4-amidinophenyl) 3-methylphenylsulfonyl OMe amino 893 N-(4-amidinophenyl) 3-methylphenylsulfonyl OH amino 894 N-(4-amidinophenyl) n-butylsulfonyl OMe amino 895 N-(4-amidinophenyl) n-butylsulfonyl OH amino 896 N-(4-amidinophenyl)-N- benzyloxycarbonyl OMe methylamino 897 N-(4-amidinophenyl)-N- benzyloxycarbonyl OH methylamino 898 N-(4-amidinophenyl)-N- n-butyloxycarbonyl OMe methylamino 899 N-(4-amidinophenyl)-N- n-butyloxycarbonyl OH methylamino 900 N-(4-amidinophenyl)-N- cyclopropylethoxy OMe methylamino carbonyl 901 N-( -amidinophenyl)-N- cyclopropylethoxy OH methylamino carbonyl 902 N-(4-amidinophenyl)-N- 4-methylphenylsulfonyl OMe methylamino 903 N-(4-amidinophenyl)-N- 4-methylphenylsulfonyl OH methylamino Example *1- • 'V .16 MS Number (M+H) + 90 N-(4-amidinophenyl)-N 3-methylphenylsulfonyl OMe methylamino 905 N-(4-amidinophenyl)-N 3-methylphenylsulfonyl OH methylamino 906 N-(4-amidinophenyl)-N n-butylsulfonyl OMe methylamino 907 N-(4-amidinophenyl)-N n-butylsulfonyl OH methylamino 908 4-amidinobenzoyl benzyloxycarbonyl OMe 909 4-amidinobenzoyl benzyloxycarbonyl OH 910 4-amidinobenzoyl n-butyloxycarbonyl OMe 911 4-amidinobenzoyl n-butyloxycarbonyl OH 912 4-amidinobenzoyl cyclopropylethoxy OMe carbonyl 913 4-amidinobenzoyl cyclopropylethoxy OH carbonyl 914 4-amidinobenzoyl 4-methylphenylsulfonyl OMe 915 4-amidinobenzoyl 4-methylphenylsulfonyl OH 916 4-amidinobenzoyl 3-methylphenylsulfonyl OMe 917 4-amidinobenzoyl 3-methylphenylsulfonyl OH 918 4-amidinobenzoyl n-butylsulfonyl OMe 919 4-amidinobenzoyl n-butylsulfonyl OH 920 4-amidinophenyl benzyloxycarbonyl OMe methylcarbonyl 921 4-amidinophenyl benzyloxycarbonyl OH methylcarbonyl 922 4-amidinophenyl n-butyloxycarbonyl OMe methylcarbonyl 923 4-amidinophenyl n-butyloxycarbonyl OH methylcarbonyl 924 4-amidinophenyl cyclopropylethoxy OMe methylcarbonyl carbonyl .16 MS (M+H) cyclopropylethoxy OH carbonyl 4-methylphenylsulfonyl OMe 4-methylphenylsulfonyl OH 3-methylphenylsulfonyl OMe 3-methylphenylsulfonyl OH n-butylsulfonyl OMe n-butylsulfonyl OH benzyloxycarbonyl OMe benzyloxycarbonyl OH n-butyloxycarbonyl OMe n-butyloxycarbonyl OH cyclopropylethoxy OMe carbonyl cyclopropylethoxy OH carbonyl 4-methylphenylsulfonyl OMe 4-methylphenylsulfonyl OH 3-methylphenylsulfonyl OMe Example »l-• < V »16 MS Number (M+H) ' 941 4-amidinophenyl- 3-methylphenylsulfonyl OH carbonylmethyl 942 4-amidinophenyl- n-butylsulfonyl OMe carbonylmethyl 943 4-amidinophenyl- n-butylsulfonyl OH carbonylmethyl Tahle 2B a »16 MS (M+H) ' benzyloxycarbony OMe 496 n-butyloxycarbony OMe 3-methylphenylsulfonyl OMe benzyloxycarbonyl OH n-butyloxycarbonyl OH 3-methylphenylsulfonyl OH 4-methylphenylsulfonyl OH 4-methylphenylsulfonyl OMe n-butylsulfonyl OH n-butylsulfonyl OMe Table 2C Example »1-Λi R 16 Number 661 4-amidinophenyl benzyloxycarbonyl 662 4-amidinophenyl benzyloxycarbonyl 663 4-amidinophenyl n-butyloxycarbonyl 664 4-amidinophenyl n-butyloxycarbonyl 665 -amidinophenyl 3-methylphenylsulfonyl 666 4-amidinophenyl 3-methylphenylsulfonyl 667 4-amidinophenyl 4-methylphenylsulfonyl 668 4-amidinophenyl 4-methylphenylsulfonyl 669 4-amidinophenyl n-butylsulfonyl 670 4-amidinophenyl n-butylsulfonyl Tafrle 2P ,16 MS (M+H) ' 722 -amidinophenyl Example ■ V »16 MS Number (M+H) ' 480 446 Example ■ V > 16 MS Number (M+H) ' 440 Example »l-ι .16 MS Number (M+H) ' Example R 1 -V >16 MS Number (M+H) ' 790 4-amidinophenyl 2-cyclopropylethoxy- OH carbonyl 791 4-amidinophenyl 2-cyclopentylethoxy- OMe carbonyl 792 4-amidinophenyl 2-cyclopentylethoxy- OH carbonyl 793 4-amidinophenyl n-propylsulfonyl OMe 794 4-amidinophenyl 2-methylphenyl- OMe sulfonyl 795 4-amidinophenyl 2-benzothienyl- OMe sulfonyl 796 4-amidinophenyl 2-benzothienyl- OMe sulfonyl 797 4-amidinophenyl 2,2,5,7,8-pentamethyl OH 3,4-dihydro-2Hbenzo- pyran-6-ylsulfonyl 798 4-amidinophenyl 3-methylphenylsulfonyl OH 486 MS (M+H) ' Example R 1 -V .16 MS Number (M+H) + 823 4-amidinophenyl 824 4-amidinophenyl 825 4-amidinophenyl 826 4-amidinophenyl 448 Example j l- ■ 'V ,16 MS Number (M+H) ' 847 4-amidinophenyl 848 4-amidinophenyl 849 4-amidinophenyl 850 4-amidinophenyl 851 4-amidinophenyl 852 4-amidinophenyl 853 4-piperidinylethyl 854 4-(BOCamidino)phenyl 855 4-(BOCamidino)phenyl 856 4-amidinophenyl 857 4-amidinophenyl 858 4-piperidinylethyl 859 -amidinophenyl 860 -amidinophenyl 861 4-amidinophenyl 862 4-amidinophenyl 863 4-amidinophenyl 864 4-amidinophenyl 865 4-amidinophenyl Example R 1 -V ,16 MS Number (M+H) ' 866 4-amidinophenyl 3-phenylpropyl- OMe sulfonyl 867 4-amidinophenyl 3-pyridylsulfonyl OMe 868 4-amidinophenyl 2-pyridylsulfonyl OMe 869 4-amidinophenyl n-butylaminosulfonyl OMe 870 4-amidinophenyl i-butylaminosulfonyl OMe 871 4-amidinophenyl t-butylaminosulfonyl OMe 872 4-amidinophenyl i-propylamino- OMe sulfonyl 873 4-amidinophenyl cyclohexylamino- OMe sulfonyl 874 4-amidinophenyl phenylaminosulfonyl OMe 875 4-amidinophenyl benzylaminosulfonyl OMe 876 4-amidinophenyl dimethylamino- OMe sulfonyl 877 2-fluoro-4-amidino- 3-methylphenyl- OMe phenyl sulfonyl 878 5-amidino-2-pyridyl n-butyloxycarbonyl OMe 879 5-amidino-2-pyridyl 3-methylphenyl- OMe sulfonyl 880 6-amidino-3-pyridyl n-butyloxycarbonyl OMe 881 6-amidino-3-pyridyl 3-methylphenyl- OMe sulfonyl 882 4-amidinophenyl phenylaminocarbonyl OMe 883 4-amidinophenyl benzylaminocarbonyl OMe 884 4-amidinophenyl n-butylaminocarbonyl OMe 885 4-amidinophenyl n-hexyloxycarbonyl OMe 886 4-amidinophenyl n-hexyloxycarbonyl OH 887 4-amidinophenyl isobutyloxycarbonyl OMe 888 4-amidinophenyl isobutyloxycarbonyl OH 889 4-amidinophenyl 2-cyclopropylethoxy- OMe carbonyl Example .1-γ ,16 MS Number (M+H) ' 890 4-amidinophenyl 2-cyclopropylethoxy- OH carbonyl 891 4-amidinophenyl 2-cyclopentylethoxy- OMe carbonyl 892 4-amidinophenyl 2-cyclopentylethoxy- OH carbonyl 893 -amidinophenyl n-propylsulfonyl OMe 894 4-amidinophenyl 2-methylphenyl- OMe sulfonyl 895 4-amidinophenyl 2-benzothienyl- OMe sulfonyl 896 4-amidinophenyl 2-benzothienyl- OMe sulfonyl 897 -amidinophenyl 2,2,5,7, 8-pentamethyl OH 3,4-dihydro-2Hbenzo- pyran-6-ylsulfonyl Tahle 3 Table 4 z i OH OH OH OH OH OEt OEt OEt OEt OEt Table 5 381 OH — N NH YC(=0)CH 2 o 396 OMe CH 2 C(=0)Y CH 2 C(=0)Y Utility The compounds of this invention possess antiplatelet efficacy, as evidenced by their activity in standard platelet aggregation assays or platelet fibrinogen binding assays, as described below. A compound is considered to be active in these assays if it has an IC 50 value of less than about 1 M. Platelet aggregation and fibrinogen binding assays which may be used to demonstrate the antiplatelet activity of the compounds of the invention are described below. Platelet Aggregation Assay; Venous blood was obtained from the arm of a healthy human donor who was drug-free and aspirin-free for at least two weeks prior to blood collection. Blood was collected into 10 mL citrated Vacutainer tubes. The blood was centrifuged for 15 minutes at 150 x g at room temperature, and platelet-rich plasma (PRP) was removed. The remaining blood was centrifuged for 15 minutes at 1500 x g at room temperature, and platelet-poor plasma (PPP) was removed. Samples were assayed on a aggregometer (PAP-4 Platelet Aggregation Profiler) , using PPP as the blank (100% transmittance) . 200 μL of PRP was added to each micro test tube, and transmittance was set to 0%. 20 μL of various agonists (ADP, collagen, arachidonate, epinephrine, thrombin) were added to each tube, and the aggregation profiles were plotted (% transmittance versus time) . The results are expressed as % inhibition of agonist-induced platelet aggregation. For the IC 5 0 evaluation, the test compounds were added at various concentrations prior to the activation of the platelets. Ester prodrugs were preincubated (10 ~3 M F.C.) with 100 IU/ml Porcine liver esterase (Sigma Chemical Co., St. Louis, MO, #E-3128) for 2 hours at 37 °C. Aliquots are then diluted in 0.1 M Tris, pH 7.4, to the desired concentrations. Aliquots of 20 μl of the esterase pretreated prodrugs are added to 200 μl of human platelet rich plasma. Samples were placed in platelet profiler (aggregometer) for 8 minutes at 37 °C, followed by the addition of 100 μM Adenosine Diphosphate, (Sigma Chemical Co., St. Louis, MO, #A-6521), to induce platelet aggregation. Platelet aggregation was allowed to proceed for 5 minutes. Percent inhibition is calculated using percent aggregation in the presence of the test compound divided by percent aggregation of control, times 100. This value is subtracted from 100, yielding percent inhibition. Calculation of IC50 is performed on a Texas Instruments TI59 with an IC50 program. Purified GPIIb/lIIa-Fibrinogen Binding ELISA The following reagents are used in the GPIIb/IIIa-fibrinogen binding ELISA: purified GPIIb/IIIa (148.8 μg/mL) ; biotinylated fibrinogen (~ 1 mg/mL or 3000 nM) ; anti-biotin alkaline phosphatase conjugate (Sigma no. A7418) ; flat-bottom, high binding, 96-well plates (Costar Cat. no. 3590); phosphatase substrate (Sigma 104) (40 mg capsules) ; bovine serum albumin (BSA) (Sigma no. A3294) ; Alkaline Phosphatase buffer - 0.1 M glycine-HCl, 1 mM MgCl 2 .6H 2 0, 1 mM ZnCl 2 , pH 10.4; Binding buffer - 20 mM Tris-HCI, 150 mM NaCl, 1 mM CaCl 2 .2H 2 0, 0.02% NaN 3 , pH 7.0; Buffer A - 50 mM Tris-HCl, 100 mM NaCl, 2 mM CaCl 2 .2H 2 0, 0.02% NaN 3 , pH 7.4; Buffer A + 3.5% BSA (Blocking buffer); Buffer A + 0.1% BSA (Dilution buffer); 2N NaOH. The following method steps are used in the GPIIb/IIIa-fibrinogen binding ELISA: Coat plates with GPIIb/IIIa in Binding buffer (125 ng/100 μL/well) overnight at 4 °C (Leave first column uncoated for non-specific binding) . Cover and freeze plates at -70 °C until used. Thaw plate 1 hour at room temperature or overnight at 4 °C. Discard coating solution and wash once with 200 μL Binding buffer per well. Block plate 2 hours at room temperature on shaker with 200 μl Buffer A + 3.5% BSA (Blocking buffer) per well. Discard Blocking buffer and wash once with 200 μL Buffer A + o.l% BSA (Dilution buffer) per well. Pipet 11 μL of test compound (10X the concentration to be tested in Dilution buffer) into duplicate wells. Pipet 11 μl Dilution buffer into non-specific and total binding wells. Add 100 μL Biotinylated fibrinogen (1/133 in Dilution buffer, final concentration = 20 nM) to each well. Incubate plates for 3 hours at room temperature on a plate shaker. Discard assay solution and wash twice with 300 μL Binding buffer per well. Add 100 uL Anti-biotin alkaline phosphatase conjugate (1/1500 in Dilution buffer) to each well. Incubate plates for 1 hour at room temperature on plate shaker. Discard conjugate and wash twice with 300 51 Binding buffer per well. Add 100 μL Phosphatase substrate (1.5 mg/ml in Alkaline phosphatase buffer) to each well. Incubate plate at room temperature on shaker until color develops. Stop color development by adding 25 μL 2N NaOH per well. Read plate at 405 nm. Blank against non-specific binding (NSB) well. % Inhibition is calculated as 100 - (Test Compound Abs/Total Abs)xl00. SUBSTITUTL SHEET(RULE26) Platelet-Fibrinogen Binding Assay: Binding of 125 I-fibrinogen to platelets was performed as described by Bennett et al. (1983) Proc. Natl. Acad. Sci. USA 80: 2417-2422, with some modifications as described below. Human PRP (h-PRP) was applied to a Sepharose column for the purification of platelet fractions. Aliquots of platelets (5 X 10 8 cells) along with 1 m calcium chloride were added to removable 96 well plates prior to the activation of the human gel purified platelets (h-GPP) . Activation of the human gel purified platelets was achieved using ADP, collagen, arachidonate, epinephrine, and/or thrombin in the presence of the ligand, 125 I-fibrinogen. The 125 I-fibrinogen bound to the activated platelets was separated from the free form by centrifugation and then counted on a gamma counter. For an IC 50 evaluation, the test compounds were added at various concentrations prior to the activation of the platelets. The compounds of Formula I of the present invention may also possess thrombolytic efficacy, that is, they are capable of lysing (breaking up) already formed platelet-rich fibrin blood clots, and thus are useful in treating a thrombus formation, as evidenced by their activity in the tests described below. Preferred compounds of the present invention for use in thrombolysis include those compounds having an IC 50 value (that is, the molar concentration of the compound capable of achieving 50% clot lysis) of less than about 1 μM, more preferably an IC 50 value of less than about 0.1 μM. Thrombolytic Assay: Venous blood was obtained from the arm of a healthy human donor who was drug-free and aspirin free for at least two weeks prior to blood collection, and placed into 10 ml citrated Vacutainer tubes. The blood was centrifuged for 15 minutes at 1500 x g at room temperature, and platelet rich plasma (PRP) was removed. To the PRP was then added 1 x 10 "3 M of the agonist ADP, epinephrine, collagen, arachidonate, serotonin or thrombin, or a mixture thereof, and the PRP incubated for 30 minutes. The PRP was centrifuged for 12 minutes at 2500 x g at room temperature. The supernatant was then poured off, and the platelets remaining in the test tube were resuspended in platelet poor plasma (PPP) , which served as a plasminogen source. The suspension was then assayed on a Coulter Counter (Coulter Electronics, Inc., Hialeah, FL) , to determine the platelet count at the zero time point. After obtaining the zero time point, test compounds were added at various concentrations. Test samples were taken at various time points and the platelets were counted using the Coulter Counter. To determine the percent of lysis, the platelet count at a time point subsequent to the addition of the test compound was subtracted from the platelet count at the zero time point, and the resulting number divided by the platelet count at the zero time point. Multiplying this result by 100 yielded the percentage of clot lysis achieved by the test compound. For the IC 50 evaluation, the test compounds were added at various concentrations, and the percentage of lysis caused by the test compounds was calculated. The compounds of Formula I of the present invention are also useful for administration in combination with anti-coagulant agents such as warfarin or heparin, or antiplatelet agents such as aspirin, piroxicam or ticlopidine, or thrombin inhibitors such as boropeptides, hirudin or argatroban, or thrombolytic agents such as tissue plasminogen activator, anistreplase, urokinase or streptokinase, or combinations thereof. The compounds of Formula I of the present invention may also be useful as antagonists of other integrins such as for example, the α v /β 3 or vitronectin receptor, c- /βι or 0. 5 /βι and as such may also have utility in the treatment and diagnosis of osteoporosis, cancer metastasis, diabetic retinopathy, rheumatoid arthritis, inflammation, and autoimmune disorders. The compounds of Formula I of the present invention may be useful for the treatment or prevention of other diseases which involve cell adhesion processes, including, but not limited to, infanimation, bone degradation, rheumatoid arthritis, asthma, allergies, adult respiratory distress syndrome, graft versus host disease, organ transplantation, septic shock, psoriasis, eczema, contact dermatitis, osteoporosis, osteoarthritis, atherosclerosis, metastasis, wound healing, diabetic retinopathy, inflammatory bowel disease and other autoimmune diseases. Table A below sets forth the antiplatelet activity of representative compounds of the present invention. The indicated compounds were tested for their ability to inhibit platelet aggregation (using platelet rich plasma (PRP) ) . The IC 50 value (the concentration of antagonist which inhibits platelet aggregation by 50% relative to a control lacking the antagonist) is shown. In Table 5 the IC 50 values are expressed as: +++ = IC 50 of <10 μM; ++ = IC 50 Of 10-50 μM; + = IC 50 Of 50-100 μM (μM = micromolar) . 326 +++ 327 (2S) +++ 328 (2S) +++ 338 (3S) + +++ 339 (3S) +++ 340 (3S) + ++ 341 (3S) +++ 342 (2S) +++ 344 (3R) +++ 345 +++ 347 (3R)tt +++ 348 (3R) +++ 350 +++ 359 +++ 362 +++ 365 +++ 368 +++ 373 ++ 371A +++ 371B +++ 374 (2S) + +++ 375* +++ 377 +++ 394 +++ 394Att +++ 400 +++ 413* +++ 415 +++ 435 +++ 436 +++ 437 +++ 438 +++ 439 +++ 440 +++ 441 +++ ^ 69 442 +++ 443 (2S) +++ 444 (2S) +++ 445 (2S) +++ 446 +++ 449A +++ 449B +++ 450 +++ 451 +++ 452 +++ 453 +++ 454 +++ 455 +++ 456 ++ 457 +++ 458A +++ 458B +++ 460A +++ 460B +++ 462 +++ 463 +++ 464 +++ 465 +++ 466 +++ 467 +++ 468 +++ 469 +++ 470 +++ 471 +++ 472 +++ 473 +++ 473A (2S) t +++ 473B (2S) tt +++ 474 +++ 475 +++ 476 +++ 477 +++ 478 +++ 479 +++ 480 +++ 481 +++ 482 +++ 483 +++ 484 +++ 485 +++ 486 +++ 487 +++ 488 +++ 489 +++ 490 +++ 491 +++ 492 +++ 493 +++ 494 +++ 495 +++ 496 +++ 504 +++ 505 +++ 506 +++ 507 +++ 508 +++ 509 +++ 510 +++ 511 +++ 512 +++ 513 +++ 514 +++ 515 +++ 516 +++ 517 +++ 518 +++ 519 +++ 520 +++ 522 +++ 523 +++ 524 +++ 525 +++ 526 +++ 527 +++ 528 +++ 529 +++ 530 +++ 531 +++ 532 +++ 533 +++ 534 +++ 535 +++ 536 +++ 537 +++ 538 +++ 539 +++ 540 +++ 541 +++ 542 +++ 543 +++ 544 +++ 545 +++ 546 +++ 547 +++ 548 +++ 549 +++ 550 +++ 551 +++ 552 +++ 553 +++ 554 +++ 555 +++ 556 +++ 587A (2S)tt +++ 588 +++ 602 +++ 611 +++ 612 +++ 613 +++ 616 +++ 651 +++ 727 +++ 729 +++ 798 +++ 829 +++ * Single diastereomer, racemic t S isomer at C5 of isoxazoline ring tt R isomer at C5 of isoxazoline ring Dosage and Formulation The compounds of the present invention can be administered in such oral dosage forms as tablets, capsules (each of which includes sustained release or timed release formulations) , pills, powders, granules, elixirs, tinctures, suspensions, syrups, and emulsions. Likewise, they may also be administered in intravenous (bolus or infusion) , intraperitoneal, subcutaneous, or intramuscular form, all using dosage forms well known to those of ordinary skill in the pharmaceutical arts. An effective but non-toxic amount of the compound desired can be employed as an anti-aggregation agent. The compounds of this invention can be administered by any means that produces contact of the active agent with the agent's site of action, glycoprotein Ilb/IIIa (GPIIb/IIIa) , in the body of a mammal. They can be administered by any conventional means available for use in conjunction with pharmaceuticals, either as individual therapeutic agents or in a combination of therapeutic agents, such as a second antiplatelet agent such as aspirin or ticlopidine which are agonist- specific. They can be administered alone, but generally administered with a pharmaceutical carrier selected on the basis of the chosen route of administration and standard pharmaceutical practice. The dosage regimen for the compounds of the present invention will, of course, vary depending upon known factors, such as the pharmacodynamic characteristics of the particular agent and its mode and route of administration; the species, age, sex, health, medical condition, and weight of the recipient; the nature and extent of the symptoms; the kind of concurrent treatment; the frequency of treatment; the route of administration, the renal and hepatic function of the patient,and the effect desired. An ordinarily skilled physician or veterinarian can readily determine and prescribe the effective amount of the drug required to prevent, counter, or arrest the progress of the condition. By way of general guidance, the daily oral dosage of each active ingredient, when used for the indicated effects, will range between about 0.001 to 1000 mg/kg of body weight, preferably between about 0.01 to 100 mg/kg of body weight per day, and most preferably between about 1.0 to 20 mg/kg/day. Intravenously, the most preferred doses will range from about 1 to about 10 mg/kg/minute during a constant rate infusion. Advantageously, compounds of the present invention may be administered in a single daily dose, or the total daily dosage may be administered in divided doses of two, three, or four times daily. The compounds for the present invention can be administered in intranasal form via topical use of suitable intranasal vehicles, or via transdermal routes, using those forms of transdermal skin patches wall known to those of ordinary skill in that art. To be administered in the form of a transdermal delivery system, the dosage administration will, of course, be continuous rather than intermittant throughout the dosage regimen. In the methods of the present invention, the compounds herein described in detail can form the active ingredient, and are typically administered in admixture with suitable pharmaceutical diluents, excipients, or carriers (collectively referred to herein as carrier materials) suitably selected with respect to the intended form of administration, that is, oral tablets, capsules, elixirs, syrups and the like, and consistent with conventional pharmaceutical practices. For instance, for oral administration in the form of a tablet or capsule, the active drug component can be combined with an oral, non-toxic, pharmaceutically acceptable, inert carrier such as lactose, starch, sucrose, glucose, methyl callulose, magnesium stearate, dicalcium phosphate, calcium sulfate, mannitol, sorbitol and the like; for oral administration in liquid form, the oral drug components can be combined with any oral, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. Moreover, when desired or necessary, suitable binders, lubricants, disintegrating agents, and coloring agents can also be incorporated into the mixture. Suitable binders include starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tragacanth, or sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes, and the like. Lubricants used in these dosage forms include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, and the like. Disintegrators include, without limitation, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like. The compounds of the present invention can also be administered in the form of liposome delivery systems, such as small unilamellar vesicles, large unilamallar vesicles, and multilamellar vesicles. Liposomes can be formed from a variety of phospholipids, such as cholesterol, stearylamine, or phosphatidylcholines. Compounds of the present invention may also be coupled with soluble polymers as targetable drug carriers. Such polymers can include polyvinylpyrrolidone, pyran copolymer, polyhydroxypropylmethacrylamide-phenol, polyhydroxyethylaspartamidephenol, or polyethyleneoxide- polylysine substituted with palmitoyl residues. Furthermore, the compounds of the present invention may be coupled to a class of biodegradable polymers useful in achieving controlled release of a drug, for example, polylactic acid, polyglycolic acid, copolymers of polylactic and polyglycolic acid, polyepsilon caprolactone, polyhydroxy butyric acid, polyorthoesters, polyacetals, polydihydropyrans, polycyanoacylates, and crosslinked or amphipathic block copolymers of hydrogels. Dosage forms (pharmaceutical compositions) suitable for administration may contain from about 1 milligram to about 100 milligrams of active ingredient per dosage unit. In these pharmaceutical compositions the active ingredient will ordinarily be present in an amount of about 0.5-95% by weight based on the total weight of the composition. The active ingredient can be administered orally in solid dosage forms, such as capsules, tablets, and powders, or in liquid dosage forms, such as elixirs, syrups, and suspensions. It can also be administered parenterally, in sterile liquid dosage forms. Gelatin capsules may contain the active ingredient and powdered carriers, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, and the like. Similar diluents can be used to make compressed tablets. Both tablets and capsules can be manufactured as sustained release products to provide for continuous release of medication over a period of hours. Compressed tablets can be sugar coated or film coated to mask any unpleasant taste and protect the tablet from the atmosphere, or enteric coated for selective disintegration in the gastrointestinal tract. Liquid dosage forms for oral administration can contain coloring and flavoring to increase patient acceptance. In general, water, a suitable oil, saline, aqueous dextrose (glucose) , and related sugar solutions and glycols such as propylene glycol or polyethylene glycols are suitable carriers for parenteral solutions. Solutions for parenteral administration preferably contain a water soluble salt of the active ingredient, suitable stabilizing agents, and if necessary, buffer substances. Antioxidizing agents such as sodium bisulfite, sodium sulfite, or ascorbic acid, either alone or combined, are suitable stabilizing agents. Also used are citric acid and its salts and sodium EDTA. In addition, parenteral solutions can contain preservatives, such as benzalkonium chloride, methyl- or propyl-paraben, and chlorobutanol. Suitable pharmaceutical carriers are described in Remington's Pharmaceutical Sciences, Mack Publishing Company, a standard reference text in this field. Representative useful pharmaceutical dosage-forms for administration of the compounds of this invention can be illustrated as follows: Capsules A large number of unit capsules are prepared by filling standard two-piece hard gelatin capsules each with 100 milligrams of powdered active ingredient, 150 milligrams of lactose, 50 milligrams of cellulose, and 6 milligrams magnesium stearate. Soft Gelatin Capsules A mixture of active ingredient in a digestable oil such as soybean oil, cottonseed oil or olive oil is prepared and injected by means of a positive displacement pump into gelatin to form soft gelatin capsules containing 100 milligrams of the active ingredient. The capsules are washed and dried. Tablets A large number of tablets are prepared by conventional procedures so that the dosage unit was 100 milligrams of active ingredient, 0.2 milligrams of colloidal silicon dioxide, 5 milligrams of magnesium stearate, 275 milligrams of microcrystalline cellulose, 11 milligrams of starch and 98.8 milligrams of lactose. Appropriate coatings may be applied to increase palatability or delay absorption. Injectable A parenteral composition suitable for administration by injection is prepared by stirring 1.5% by weight of active ingredient in 10% by volume propylene glycol and water. The solution is made isotonic with sodium chloride and sterilized. Suspension An aqueous suspension is prepared for oral administration so that each 5 mL contain 100 mg of finely divided active ingredient, 200 mg of sodium carboxymethyl cellulose, 5 mg of sodium benzoate, 1.0 g of sorbitol solution, U.S.P., and 0.025 mL of vanillin. The compounds of the present invention may be administered in combination with a second therapeutic agent selected from: an anti-coagulant agent such as warfarin or heparin; an anti-platelet agent such as aspirin, piroxicam or ticlopidine; a thrombin inhibitor such as a boropeptide thrombin inhibitor, or hirudin; or a thrombolytic agent such as plasminogen activators, such as tissue plasminogen activator, anistreplase, urokinase or streptokinase. The compound of Formula I and such second therapeutic agent can be administered separately or as a physical combination in a single dosage unit, in any dosage form and by various routes of administration, as described above. The compound of Formula I may be formulated together with the second therapeutic agent in a single dosage unit (that is, combined together in one capsule, tablet, powder, or liquid, etc.) . hen the compound o: Formula I and the second therapeutic agent are not formulated together in a single dosage unit, the compound of Formula I and the second therapeutic agent (anti-coagulant agent, anti-platelet agent, thrombin inhibitor, and/or thrombolytic agent) may be administered essentially at the same time, or in any order; for example the compound of Formula I may be administered first, followed by administration of the second agent (anti-coagulant agent, anti-platelet agent, thrombin inhibitor, and/or thrombolytic agent) . When not administered at the same time, preferably the administration of the compound of Formula I and the second therapeutic agent occurs less than about one hour apart. A preferable route of administration of the compound of Formula I is oral. Although it is preferable that the compound of Formula I and the second therapeutic agent (anti-coagulant agent, anti-platelet agent, thrombin inhibitor, and/or thrombolytic agent) are both administered by the same route (that is, for example, both orally) , if desired, they may each be administered by different routes and in different dosage forms (that is, for example, one component of the combination product may be administered orally, and another component may be administered intravenously) . The dosage of the compound of Formula I when administered alone or in combination with a second therapeutic agent may vary depending upon various factors such as the pharmacodynamic characteristics of the particular agent and its mode and route of administration, the age, health and weight of the recipient, the nature and extent of the symptoms, the kind of concurrent treatment, the frequency of treatment, and the effect desired, as described above. Although the proper dosage of the compound of Formula I when administered in combination with the second therapeutic agent will be readily ascertainable by a medical practitioner skilled in the art, once armed with the present disclosure, by way of general guidance, where the compounds of this invention are combined with anti-coagulant agents, for example, a daily dosage may be about 0.1 to 100 milligrams of the compound of Formula I and about 1 to 7.5 milligrams of the anti- coagulant, per kilogram of patient body weight. For a tablet dosage form, the novel compounds of this invention generally may be present in an amount of about 1 to 10 milligrams per dosage unit, and the anti¬ coagulant in an amount of about 1 to 5 milligrams per dosage unit. Where the compounds of Formula I are administered in combination with a second anti-platelet agent, by way of general guidance, typically a daily dosage may be about 0.01 to 25 milligrams of the compound of Formula I and about 50 to 150 milligrams of the additional anti-platelet agent, preferably about 0.1 to 1 milligrams of the compound of Formula I and about 1 to 3 milligrams of antiplatelet agents, per kilogram of patient body weight. Further, by way of general guidance, where the compounds of Formula I are adminstered in combination with thrombolytic agent, typically a daily dosage may be about 0.1 to 1 milligrams of the compound of Formula I, per kilogram of patient body weight and, in the case of the thrombolytic agents, the usual dosage of the thrombolyic agent when administered alone may be reduced by about 70-80% when administered with a compound of Formula I. Where two or more of the foregoing second therapeutic agents are administered with the compound of Formula I, generally the amount of each component in a typical daily dosage and typical dosage form may be reduced relative to the usual dosage of the agent when administered alone, in view of the additive or synergistic effect of the therapeutic agents when administered in combination. Particularly when provided as a single dosage unit, the potential exists for a chemical interaction between the combined active ingredients. For this reason, when the compound of Formula I and a second therapeutic agent are combined in a single dosage unit they are formulated such that although the active ingredients are combined in a single dosage unit, the physical contact between the active ingredients is minimized (that is, reduced) . For example, one active ingredient may be enteric coated. By enteric coating one of the active ingredients, it is possible not only to minimize the contact between the combined active ingredients, but also, it is possible to control the release of one of these components in the gastrointestinal tract such that one of these components is not released in the stomach but rather is released in the intestines. One of the active ingredients may also be coated with a sustained- release material which effects a sustained-release throughout the gastrointestinal tract and also serves to minimize- physical contact between the combined active ingredients. Furthermore, the sustained-released component can be additionally enteric coated such that the release of this component occurs only in the intestine. Still another approach would involve the formulation of a combination product in which the one component is coated with a sustained and/or enteric release polymer, and the other component is also coated with a polymer such as a lowviscosity grade of hydroxypropyl methylcellulose (HPMC) or other appropriate materials as known in the art, in order to further separate the active components. The polymer coating serves to form an additional barrier to interaction with the other component. These as well as other ways of minimizing contact between the components of combination products of the present invention, whether administered in a single dosage form or administered in separate forms but at the same time by the same manner, will be readily apparent to those skilled in the art, once armed with the present disclosure. The present invention also includes pharmaceutical kits useful, for example, in the inhibition of platelet aggregation, the treatment of blood clots, and/or the treatment of thromboembolic disorders, which comprise one or more containers containing a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I. Such kits may further include, if desired, one or more of various conventional pharmaceutical kit components, such as, for example, containers with one or more pharmaceutically acceptable carriers, additional containers, etc., as will be readily apparent to those skilled in the art. Instructions, either as inserts or as labels, indicating quantities of the components to be administered, guidelines for administration, and/or guidelines for mixing the components, may also be included in the kit. In the present disclosure it should be understood that the specified materials and conditions are important in practicing the invention but that unspecified materials and conditions are not excluded so long as they do not prevent the benefits of the invention from being realized.

Claims: CLAIMS WHAT IS CLAIMED IS: 1. A compound of Formula I: or pharmaceutically acceptable salt form thereof wherein: b is a single or double bond; R 1 is selected from R 2 (R 3 )N(CH 2 ) g Z- , R 2 (R 3 )N(R 2 N=)CN(R 2 ) (CH 2 ) q Z-, piperazinyl- (CH 2 ) q Z- or Z is selected from O, S, S(=0), or S(=0) 2 ; R 2 and R 3 are independently selected from: H, Ci-Cio alkyl, C 2 -C 6 alkenyl, C 3 -Cn cycloalkyl, C 4 -C 11 cycloalkylalkyl, Cβ-Cio aryl, C -Cn arylalkyl, C 2 -C alkylcarbonyl, Cg-Cio arylcarbonyl, C 2 -Cιo alkoxycarbonyl, C 4 -C 11 cycloalkoxycarbonyl, C 7 -C 11 bicycloalkoxycarbonyl, Cβ-Cio aryloxycarbonyl , aryl (Ci- Cio alkoxy) carbonyl , Ci-Cβ alkylcarbonyloxy (C 1 -C 4 alkoxy) carbonyl , Cg-Cio arylcarbonyloxy(C 1 -C 4 alkoxy) carbonyl, C 4 -C 11 cycloalkylcarbonyloxy(Ci-C 4 alkoxy) carbonyl; U is selected from: a single bond, - (C 1 -C 7 alkyl) -, - (C -C 7 alkenyl) - , - (C 2 -C 7 alkynyl) -, - (aryl) - substituted with 0-3 R 6a , or -(pyridyl)- substituted with 0-3 R 6a ; V is selected from: a single bond; - (C 1 -C 7 alkyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; - (C 2 -C 7 alkenyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; - (C 2 -C 7 alkynyl)-, substituted with 0-2 groups independently selected from R 6 or R 7 ; -(aryl)-, substituted with 0-2 groups independently selected from R 6 or R 7 ; -(pyridyl)-, substituted with 0-2 groups independently selected from R 6 or R 7 ; or -(pyridazinyl)-, substituted with 0-2 groups independently selected from R 6 or R 7 ; W is selected from: a single bond, -(C 1 -C 7 alkyl)-, -(C 2 -C 7 alkenyl)-, - (C 2 -C 7 alkynyl) - , or - ( C (R 5 ) 2 ) nC (=0) N (R 5a ) - ; X is selected from: a single bond; - (C 1 -C 7 alkyl)-, substituted with 0-3 groups independently selected from R 4 , R 8 or R 14 ; - (C 2 -C 7 alkenyl)-, substituted with 0-3 groups independently selected from R 4 , R 8 or R 14 ; - (C 2 -C 7 alkynyl)-, substituted with 0-2 groups independently selected from R 4 , R 8 or R 14 ; or Y is selected from hydroxy, Ci to Cio alkyloxy, C 3 to Cn cycloalkyloxy, C to Cio aryloxy, C 7 to Cn aralkyloxy, C 3 to Cio alkylcarbonyloxyalkyloxy, C 3 to Cio alkoxycarbonyloxyalkyloxy, C 2 to Cio alkoxycarbonylalkyloxy, C 5 to Cι 0 cycloalkylcarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonylalkyloxy, C 7 to Cn aryloxycarbonylalkyloxy, Cβ to C i2 aryloxycarbonyloxyalkyloxy, Cβ to C 12 arylcarbonyloxyalkyloxy, C 5 to Cio alkoxyalkylcarbonyloxyalkyloxy, C 5 to Cio (5-alkyl- 1, 3-dioxa-cyclopenten-2-one-yl)methyloxy, Cio to C14 (5-aryl-1,3-dioxa-cyclopenten-2-one-yl)methyloxy; or (R 2 ) (R 3 )N- (Ci-Cj L o alkoxy)-; R 4 and R 4b are independently selected from H, C 1 -C 10 alkyl, hydroxy, C 1 -C 10 alkoxy, nitro, C 1 -C1 0 alkylcarbonyl, or -N(R 12 )R 13 ; R 5 is selected from H, Cι-C 8 alkyl, C 2 -C 6 alkenyl, C 3 -Cn cycloalkyl, C 4 -Cn cycloalkylmethyl, Cβ-Cio aryl, C 7 -C 11 arylalkyl, or C 1 -C 10 alkyl substituted with 0-2 R 4b ; R 5a is selected from hydrogen, hydroxy, Ci to Cβ alkyl, C 2 to β alkenyl, C 3 to Cn cycloalkyl, C to Cn cycloalkylmethyl, Ci-Cβ alkoxy, benzyloxy, ζ to Cio aryl, heteroaryl, heteroarylalkyl, C 7 to Cn arylalkyl, adamantylmethyl or C 1 -C 10 alkyl substituted with 0-2 R 4b ; alternately, R 5 and R 5a can be taken together to be 3- azabicyclononyl, 1-piperidinyl, 1-morpholinyl or 1- piperazinyl, each being optionally substituted with C± - Cβ alkyl, Cβ-Cio aryl, heteroaryl, C 7 -Cn arylalkyl, Ci-Cβ alkylcarbonyl, C 3 -C 7 cycloalkylcarbonyl, Ci-Cβ alkoxycarbonyl, C 7 -C arylalkoxycarbonyl, Ci-Cς alkylsulfonyl or Cβ-Cio arylsulfonyl; R 5b is selected from Ci-Cβ alkyl, C 2 -Cg alkenyl, C 3 -Cn cycloalkyl, C 4 -C 11 cycloalkylmethyl, Cβ-Cio aryl, C 7 -C 11 arylalkyl, or Cι-Cι 0 alkyl substituted with 0-2 R 4b ; R 6 is selected from H, C 1 -C 10 alkyl, hydroxy, Cι-Cι 0 alkoxy, nitro, C 1 -C 0 alkylcarbonyl, -N(R 12 )R 13 , cyano, halo, CF 3 , CHO, C0 2 R 5 , C(=0)R 5a , CONR 5 R 5a , OC(=0)R 5a , OC(=0)OR 5b , OR 5a , OC(=0)NR 5 R 5a , OCH 2 C0 2 R 5 , C0 CH 2 C0 2 R 5 , N0 2 , NR 5a C(=0)R 5a , NR 5a C(=0)OR 5b , NR 5a C(=0)NR 5 R 5 , NR 5a S0 2 NR 5 R 5a , NR 5a S0 2 R 5 , S(0) p R 5a , Sθ 2 R 5 R 5a , C 2 to C 6 alkenyl, C 3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl; β to Cio aryl optionally substituted with 1-3 groups selected from halogen, Ci-Cε alkoxy, Ci-Cβ alkyl, CF 3 , S(0)mMe, or -NMe 2 ; C 7 to Cn arylalkyl, said aryl being optionally substituted with 1-3 groups selected from halogen, Ci-Cβ alkoxy, Cι-C 6 alkyl, CF , S(0)mMe, or -NMe 2 ; methylenedioxy when R 6 is a substituent on aryl; or a 5-10 membered heterocyclic ring containing 1-3 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R 7 ; R 6a is selected from C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halo, CF 3 , N0 2 , or NR 12 R 13 ; R 7 is selected from H, C 1 -C 10 alkyl, hydroxy, C 1 -C 10 alkoxy, nitro, C 1 -C 10 alkylcarbonyl, -N(R 12 )R 13 , cyano, halo, CF 3 , CHO, C0 2 R 5 , C(=0)R 5a , C0NR 5 R 5a , 0C(=0)R 5a , 0C(=0)0R 5b , 0R 5a , 0C(=0)NR 5 R 5a , 0CH 2 C0 2 R 5 , C0 2 CH 2 C0 2 R 5 , N0 2 , NR 5a C(=0)R 5a , NR 5a C(=0)0R 5b , NR 5a C(=0)NR 5 R 5a , NR 5a S0 NR 5 R 5a , NR 5a S0 R 5 , S(0) p R 5a , S0 2 NR 5 R 5a , C 2 to β alkenyl, C 3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl, β to Cio aryl, or C 7 to Cn arylalkyl; R 8 is selected from: H; R δ ; C 1 -C 10 alkyl, substituted with 0-3 R 6 ; C 2 -Cιo alkenyl, substituted with 0-3 R 6 ; C 2 -C 10 alkynyl, substituted with 0-3 R 6 ; C 3 -C 8 cycloalkyl, substituted with 0-3 R 6 ; C 5 -C 6 cycloalkenyl, substituted with 0-2 R 6 ; aryl, substituted with 0-2 R 6 ; 5-10 membered heterocyclic ring containing 1-3 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R 6 ; R 12 and R 13 are independently H, Cι-Cι 0 alkyl, Cι-Cι 0 alkoxycarbonyl, Cι-Cι 0 alkylcarbonyl, Ci-Cio alkylsulfonyl, aryl(Cι-Cιo alkyl) sulfonyl, arylsulfonyl, aryl, C 2 "C 6 alkenyl, C 3 -C 11 cycloalkyl, C 4 -C 11 cycloalkylalkyl, C 7 -C 11 arylalkyl, C 2 -C 7 alkylcarbonyl, C 7 -C u arylcarbonyl, C 2 -C 10 alkoxycarbonyl, C -C 11 cycloalkoxycarbonyl, C 7 -C 11 bicycloalkoxycarbonyl, C 7 -C aryloxycarbonyl, heteroarylcarbonyl, heteroarylalkylcarbonyl or aryl (Ci-Cio alkoxy)carbonyl; R 14 is selected from H, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 1 -C 10 alkoxy, aryl, heteroaryl o C 1 -C 10 alkoxycarbonyl, C0 2 R 5 or -C(=0)N(R 5 )R 5a ; R 15 is selected from: H; R 6 ; C 1 -C 10 alkyl, substituted with 0-8 R 6 ; C 2 -C 10 alkenyl, substituted with 0-6 R 6 ; C 1 -C 10 alkoxy, substituted with 0-6 R 6 ; aryl, substituted with 0-5 R 6 ; 5-6 membered heterocyclic ring containing 1-2 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-5 R 6 ; C 1 -C 10 alkoxycarbonyl substituted with 0-8 R 6 ; CO 2 R 5 ; or -C(=0)N(R 5 )R 5a ; provided that when b is a double bond, only one of R 14 or R 15 is present; n is 0-4; q is 2-7 r is 0-3, provided that n, q, and r are chosen such that the number of in-chain atoms between R 1 and Y is in the range of 8-18. 2. A compound of Claim 1 of Formula II: wherein: R 1 is selected from R 2 HN(CH 2 ) q 0- , R 2 HN(R 2 N=)CNH(CH 2 ) q 0-, piperazinyl- (CH 2 )qO- , or R 2 is selected from H, aryl(Cι-Cιo alkoxy) carbonyl, Ci-Cio alkoxycarbonyl; R 8 is selected from H, Ci-Cio alkyl, C 2 -Cιo alkenyl, C 3 -C 8 cycloalkyl, C 5 -C 6 cycloalkenyl, aryl, 5-6 membered heterocyclic ring containing 1-2 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated; R 6 and R 7 are selected from H, Ci-Cio alkyl, hydroxy, Ci-Cio alkoxy, nitro, Ci-Cio alkylcarbonyl, -N(R 12 )R 13 , cyano, or halo. 3. A compound of Claim 2 wherein: X is selected from: a single bond; - (Cι-C 7 alkyl)-, substituted with 0-2 groups independently selected from R 4 , R 8 or R 14 ; - (C 2 -C 7 alkenyl)-, substituted with 0-2 groups independently selected from R 4 , R 8 or R 14 ; -(C 2 -C 7 alkynyl)-, substituted with 0-2 groups independently selected from R 4 , R 8 or R 14 ; R 8 is selected from H, Ci-Cβ alkyl, C 2 -Cg alkenyl, 3 -C 8 cycloalkyl, C 5 -C 6 cycloalkenyl, aryl, 5-6 membered heterocyclic ring containing 1-2 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated. A compound of Claim 2 wherein: R 1 V is phenylene or pyridylene; n is 1 or 2; X is - (Cι-C 2 ) alkyl- substituted with 0-2 R 4 Y is selected from: hydroxy; Ci to Cio alkoxy; methylcarbonyloxymethoxy- ; ethylcarbonyloxymethoxy- ; t-butylcarbonyloxymethoxy- ; cyclohexylcarbonyloxymethoxy- ; 1- (methylcarbonyloxy) ethoxy- ; 1- (ethylcarbonyloxy) ethoxy- ; 1- (t-butylcarbonyloxy) ethoxy- ; 1- (cyclohexylcarbonyloxy) ethoxy- ; i-propyloxycarbonyloxymethoxy- ; t-butyloxycarbonyloxymethoxy- ; 1- (i-propyloxycarbonyloxy)ethoxy- ; 1- (cyclohexyloxycarbonyloxy) ethoxy- ; 1- ( -butyloxycarbonyloxy) ethoxy- ; dimethylaminoethoxy- ; diethylaminoethoxy- ; (5-methyl-1,3- ioxacyclopenten-2-on-4-yl)methoxy- ; (5- (t-butyl) -1,3-dioxacyclopenten-2-on-4- yl)methoxy- ; (1, 3-dioxa-5-phenyl-cyclopenten-2-on-4-yl)methoxy- ; 1- (2- (2-methoxypropyl) carbonyloxy) ethoxy- ; R 4 is -NR 12 R 13 ; R 12 is H, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkylsulfonyl, arylalkylsulfonyl, arylsulfonyl, benzyl, benzoyl, phenoxycarbonyl, benzyloxycarbonyl, arylalkylsulfonyl, pyridylcarbonyl, or pyridylmethylcarbonyl; R 13 is H. 5. A compound of Claim 1, or a pharmaceutically acceptable salt form thereof, selected from: 5 (R, S) -3- [ [4- (2-piperidin-4-yl) ethoxyphenyl] isoxazolin- 5-yl] acetic acid; 5 (R, S) -N- (butanesulfonyl) - - {3- [4- (2-piperidin-4- yl) ethoxyphenyl] isoxazolin-5-yl}glycine; 5 (R, S) -N- ( a-toluenesulfonyl) -L- {3- [4- (2-piperidin-4- yl)ethoxyphenyl] isoxazolin-5-yljglycine; 5 (R, S) -N- [ (benzyloxy) carbonyl] -L- {3- [4- (2-piperidin-4- yl)ethoxyphenyl] isoxazolin-5-yl}glycine; 5 (R, S) -N- (pentanoyl) -L- {3- [4- (2-piperidin-4-yl)ethox¬ yphenyl] isoxazolin-5-yljglycine; 5 (#,£>) -3- { [4- (piperidin-4-yl)methoxyphenyl] isoxazolin-5- yl}propanoic acid; 2 (R, S) -5 (R, S) -N- (butanesulfonyl)amino- {3- [4- (piperidin- 4-yl)methoxyphenyl] isoxazolin-5-yl}propanoic acid; 2 (R, S) -5 (R, S) -N- (α-toluenesulfonyl) amino- {3- [4- (piperi- din-4-yl)methoxyphenyl] isoxazolin-5-yl}propanoic acid; 2 (R, S) -5 (R, S) -N- [ (benzyloxy)carbonyl]amino- {3- [4- (piper¬ idin-4-yl)methoxyphenyl] isoxazolin-5-yl}propanoic acid; 2 (R, S) -5 (R, S) -N- (pentanoyl)amino- {3- [4- (piperidin- - yl)methoxyphenyl] isoxazolin-5-yl}propanoic acid. 6. A compound of Formula I: or a pharmaceutically acceptable salt form thereof wherein: b is a single or double bond; R 1 is selected from R a (R 3 )N-, R 2 (R 3 )N(R 2 N=) C- , R 2a (R 3 )N(CH 2 )qZ-, R 2 (R 3 )N(R 2 N=) C(CH 2 ) g Z- , R (R 3 )N(R 2 N=)CN(R 2 ) -, Z is selected from: a bond, O, S, S (=0) , S(=0) 2 #* R 2 and R 3 are independently selected from: H, Ci-Cio alkyl, C 3 -C 6 alkenyl, C 3 -Cn cycloalkyl, C 4 -C 11 cycloalkylalkyl, C 6 -Cιo aryl, C 7 -C n arylalkyl, C 2 -C 7 alkylcarbonyl, C7-C 11 arylcarbonyl, C 2 -C 10 alkoxycarbonyl, C 4 -C 11 cycloalkoxycarbonyl, C 7 -C 11 bicycloalkoxycarbonyl, C 7 -C 11 aryloxycarbonyl, aryl (Ci-Cio alkoxy) carbonyl, Ci-Cg alkylcarbonyloxy(Ci-C 4 alkoxy)carbonyl, Cg-Cio arylcarbonyloxy(Ci-C 4 alkoxy)carbonyl, C 4 -Cn cycloalkylcarbonyloxy(Ci-C 4 alkoxy)carbonyl; R 2a is R 2 or R (R 3 )N(R 2 N=)C- ; U is selected from: a single bond, - ( C 1 - C 7 alkyl ) - , - (C 2 -C 7 alkenyl) - , - (C 2 -C 7 alkynyl) - , - (aryl) - substituted with 0-3 R 6a , or - (pyridyl) - substituted with 0-3 R 6a ; V is selected from: a single bond; - (C 1 -C 7 alkyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; -(C 2 -C 7 alkenyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; - (C 2 -C 7 alkynyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; - (phenyl) -Q- , said phenyl substituted with 0-2 groups independently selected from R 6 or R 7 ; - (pyridyl) -Q- , said pyridyl substituted with 0-2 groups independently selected from R 6 or R 7 ; or - (pyridazinyl) -Q- , said pyridazinyl substituted with 0-2 groups independently selected from R 6 or R 7 ' Q is selected from a single bond, -0-, -S(0) m -, -N(R 12 )-, -(CH 2 ) m -, -C(=0)-, -N(R 5a )C(=0) -, -C(=0)N(R 5a ) -, -CH 2 0-, -OCH 2 -, -CH 2 N(R 12 )-, -N(R 12 )CH 2 -, -CH 2 C(=0)-, -C(=0)CH 2 -, -CH 2 S(0) m -, or -S(0) m CH 2 -, provided that when b is a single bond, and R 1 -U-V- is a substituent on C5 of the central 5-membered ring of Formula I, then Q is not -0-, -S(0) m -, -N(R 12 )-, -C(=0)N(R 5a ) -, -CH 2 O-, CH 2 N(R 12 )- or -CH 2 S ( 0 ) m -; W is selected from: - ( C (R ) 2 ) n C (=0) N (R 5a ) - , or - C (=0) - N (R 5a ) - ( C (R 4 ) 2 ) n - ; X is selected from: a single bond, - (C(R 4 ) 2 )n'C(R 4 ) (R 8 ) -C(R 4 ) (R 4a ) -, with the proviso that when n is 0 or 1, then at least one of R a or R 8 is other than H or methyl; Y is selected from hydroxy, Ci to Cio alkyloxy, C 3 to Cn cycloalkyloxy, Cg to Cio aryloxy, C 7 to Cn aralkyloxy, C 3 to Cio alkylcarbonyloxyalkyloxy, C 3 to Cio alkoxycarbonyloxyalkyloxy, C2 to Cio alkoxycarbonylalkyloxy, C 5 to Cio cycloalkylcarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonylalkyloxy, C 7 to Cn aryloxycarbonylalkyloxy, Cβ to C 12 aryloxycarbonyloxyalkyloxy, Cs to C 12 arylcarbonyloxyalkyloxy, C 5 to Cio alkoxyalkylcarbonyloxyalkyloxy, C 5 to Cio (5-alkyl- 1, 3-dioxa-cyclopenten-2-one-yl)methyloxy, Cio to C 14 (5-aryl-1,3-dioxa-cyclopenten-2-one-yl)methyloxy, (R 2 ) (R 3 )N- (C 1 -C 10 alkoxy) -; R 4 is selected from H, C 1 -C 10 alkyl, C 1 -C 10 alkylcarbonyl, aryl, arylalkyl, cycloalkyl, or cycloalkylalkyl; alternately, two R 4 groups on adjacent carbon atoms may join to form a bond thereby to form a carbon-carbon double or triple bond between such adjacent carbon atoms; R 4a is selected from H, hydroxy, Ci-Cio alkoxy, nitro, N(R 5 )R 5a , -N(R 12 )R 13 , -N(R 16 )R 17 , Ci-Cio alkyl substituted with 0-3 R 6 , aryl substituted with 0-3 R 6 , or i-Cio alkylcarbonyl; R 4 is selected from H, Ci-C alkyl, C 2 "Cg alkenyl, C 2 - Cg alkynyl, C 3 -C 7 cycloalkyl, C 7 -C 14 bicycloalkyl, hydroxy, Ci-Cg alkoxy, Ci-C alkylthio, Ci-Cg alkylsulfinyl, Ci-Cg alkylsulfonyl, nitro, Ci-Cg alkylcarbonyl, C 6 -Cι 0 aryl, -N(R 12 )R 13 ; halo, CF 3/ CN, Ci-Cg alkoxycarbonyl, carboxy, piperidinyl, morpholinyl or pyridinyl; R 5 is selected from H, Ci-Cβ alkyl, C 3 -Cg alkenyl, C 3 -C 11 cycloalkyl, C 4 -C 11 cycloalkylmethyl, Cg-Cio aryl, C 7 -C 11 arylalkyl, or C 1 -C 10 alkyl substituted with 0-2 R 4b ; R 5a is selected from hydrogen, hydroxy, Ci to β alkyl, C 3 -Cg alkenyl, C 3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl, Ci-Cg alkoxy, benzyloxy, Cg to Cio aryl, heteroaryl, heteroarylalkyl, C 7 to Cn arylalkyl, adamantylmethyl, or C 1 -C 10 alkyl substituted with 0-2 R 4b ; alternately, R 5 and R 5a when both are substituents on the same nitrogen atom (as in -NR 5 R 5a ) can be taken together with the nitrogen atom to which they are attached to form 3-azabicyclononyl, 1,2,3,4- tetrahydro-1-quinolinyl, 1,2,3,4-tetrahydro-2- isoquinolinyl, 1-piperidinyl, 1-morpholinyl, 1- pyrrolidinyl, thiamorpholinyl, thiazolidinyl or 1- piperazinyl, each being optionally substituted with Ci-Cg alkyl, Cg-Cio aryl, heteroaryl, C 7 -Cn arylalkyl, Ci-Cg alkylcarbonyl, C 3 -C 7 cycloalkylcarbonyl, Ci-C alkoxycarbonyl, C 7 -C 11 arylalkoxycarbonyl, Ci-Cg alkylsulfonyl or Cg-Cio arylsulfonyl; R 5b is selected from Ci-Cβ alkyl, C 2 -Cg alkenyl, C 3 -C 11 cycloalkyl, C 4 -C 11 cycloalkylmethyl, C -Cio aryl, C 7 -C 11 arylalkyl, or C 1 -C 10 alkyl substituted with 0-2 R 4b ; R 6 is selected from H, C 1 -C 10 alkyl, hydroxy, C 1 -C 10 alkoxy, nitro, C 1 -C 10 alkylcarbonyl, -N(R 1 )R 13 , cyano, halo, CF 3 , CHO, C0 2 R 5 , C(=0)R 5a , CONR 5 R 5a , OC(=0)R 5a , OC(=0)OR 5b , OR 5a , OC(=0) R 5 R 5a , OCH 2 C0 2 R 5 , C0 2 CH 2 C0 2 R 5 , N0 2 , NR 5a C(=0)R 5a , NR 5a C(=0)OR 5b , NR 5a C(=0)NR 5 R 5a , NR 5 S0 2 NR 5 R 5a , NR 5a S0 2 R 5 , S(0) p R 5a , S0 2 NR 5 R 5a , SiMe 3 , C 2 to Cg alkenyl, C 3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl; Cg to Cio aryl optionally substituted with 1-3 groups selected from halogen, Ci-Cg alkoxy, Ci-Cg alkyl, CF 3 , S(0)mMe, or -NMe 2 ; C 7 to Cn arylalkyl, said aryl being optionally substituted with 1-3 groups selected from halogen, Ci-Cg alkoxy, Ci-Cg alkyl, CF 3 , S(0)mMe, or -NMe 2 ; methylenedioxy when R 6 is a substituent on aryl; or a 5-10 membered heterocyclic ring containing 1-3 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R 7 ; R 6a is selected from C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halo, CF 3 , N0 2 , or NR 12 R 13 ; R 7 is selected from H, C 1 -C 10 alkyl, hydroxy, C 1 -C1 0 alkoxy, nitro, C 1 -C 10 alkylcarbonyl, -N(R 12 )R 13 , cyano, halo, CF 3 , CH0, C0 2 R 5 , C(=0)R 5a , C0NR 5 R 5a , 0C(=0)R 5a , OC(=0)OR 5b , OR 5a , OC(=0)NR 5 R 5a , 0CH 2 C0 2 R 5 , C0 2 CH 2 C0 2 R 5 , N0 2 , NR 5a C(=0)R 5a , NR 5a C(=0)0R 5b , NR 5a C(=0)NR 5 R 5a , NR 5a S0 2 NR 5 R 5a , NR 5a S0 R 5 , S(0) p R 5a , Sθ 2 NR 5 R 5a , C 2 to Cg alkenyl, C 3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl, Cg to Cio aryl, or C 7 to Cn arylalkyl; R 8 is selected from: R 6 ; C 1 -C 10 alkyl, substituted with 0-3 R 6 ; C 2 -C 10 alkenyl, substituted with 0-3 R 6 ; C 2 -C 10 alkynyl, substituted with 0-3 R 6 ; C 3 -C 8 cycloalkyl, substituted with 0-3 R 6 ; s-Cg cycloalkenyl, substituted with 0-3 R 6 ; aryl, substituted with 0-3 R 6 ; 5-10 membered heterocyclic ring containing 1-3 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R 6 ; R 12 and R 13 are independently H, C 1 -C 10 alkyl, C1-C 10 alkoxycarbonyl, C 1 -C 10 alkylcarbonyl, C 1 -C 10 alkylsulfonyl, aryl(Cι-Cιo alkyl) sulfonyl, arylsulfonyl, a yl(C 2 "Cιo alkenyl) sulfonyl, heteroarylsulfonyl, aryl, C 2 -Cg alkenyl, C 3 -C 11 cycloalkyl, C -Cn cycloalkylalkyl, C7-C 11 ary l a lk y l , C 7 -C 11 arylcarbonyl, C 4 -C 11 cycloalkoxycarbonyl, C 7 - Cn bicycloalkoxycarbonyl, C 7 -C 11 aryloxycarbonyl, heteroarylcarbonyl, heteroarylalkylcarbonyl, or aryl (Ci-Cio alkoxy) carbonyl, wherein said aryls are optionally substituted with 0-3 substituents selected from the group consisting of: C1-C 4 alkyl, 1-C 4 alkoxy, halo, CF 3 , and N0 ; R 14 is selected from H, C1-C10 alkyl, C 2 -Cιo alkenyl, C2- 10 alkynyl, C1-C10 alkoxy, aryl, heteroaryl or C1-C10 alkoxycarbonyl, C0 2 R 5 or -C (=0) N(R 5 ) R 5a ; R 15 is selected from: H; R 6 ; -C0 2 R 5 ; -C(=0)N(R 5 ) R5 ; C1-C10 alkoxycarbonyl substituted with 0-2 R 6 ; C1-C10 alkyl, substituted with 0-3 R 6 ; C 2 -C o alkenyl, substituted with 0-3 R 6 ; C1-C10 alkoxy, substituted with 0-3 R 6 ; aryl, substituted with 0-3 R 6 ; or 5-10 membered heterocyclic ring containing 1-3 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R 6 ; provided that when b is a double bond, only one of R 14 or R 15 is present; R 16 is selected from: -C(=0) -0-R 18a , -C(=0) -R 18b , -C(=0)N(R 18b ) 2 , -C(=0)NHS0 2 R 18 , -C(=0)NHC(=0)R 18b , -C(=0)NHC(=0)0R 18a , -C (=0) NHS0 2 NHR 18b , -C(=S) -NH-R 18b , -NH-C(=0) -0-R 18a , -NH-C(=0) -R 18b , -NH-C(=0) -NH-R 18b , -S0 -0-R 18a , -S0 2 -R 18a , -S0 2 -N(18 b ) 2 , -S0 -NHC(=0)018 b , -P(=S) (0R 18a ) 2 , -P(=0) (0R 18a ) 2 , -P(=S) (R 18a ) 2 , -P(=0) (R 18a ) 2 , or R 17 is selected from: H, Ci-Cio alkyl, C 2 -Cg alkenyl, C 3 Cn cycloalkyl, C 4 -C 15 cycloalkylalkyl, aryl, aryl (Ci-Cio alkyl) - ; Ri8a i s selected from: Cι-C 8 alkyl substituted with 0-2 R 19 , C 2 -Cβ alkenyl substituted with 0-2 R 19 , C 2 -C 8 alkynyl substituted with 0-2 R 19 , C 3 -C 8 cycloalkyl substituted with 0-2 R 19 , aryl substituted with 0-4 R 19 , aryl(Cι-Cg alkyl)- substituted with 0-4 R 19 , a 5-10 membered heterocyclic ring system having 1-3 heteroatoms selected independently from 0, S, and N, said heterocyclic ring being substituted with 0-4 R 19 , Ci-Cg alkyl substituted with a 5-10 membered heterocyclic ring system having 1-3 heteroatoms selected independently from 0, S, and N, said heterocyclic ring being substituted with 0-4 R 19 ; R i8b i s selected from R 18a or H; R 19 is selected from H, halogen, CF 3 , CN, N0 2 , NR 12 R 13 , Cι-C 8 alkyl, C -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 - n cycloalkyl, C 4 -Cn cycloalkylalkyl, aryl, aryl(Cι-Cg alkyl)-, Ci-Cg alkoxy, or C 1 -C 4 alkoxycarbonyl; n is 0-4; q is 1-7; r is 0-3; provided that n, q and r are chosen such that the number of in-chain atoms connecting R 1 and Y is in the range of 8-18. 7. A compound of Claim 6 of Formula la: wherein: Z is selected from a bond, 0, or S; R 2 is selected from H, aryl(Ci-Cio alkoxy)carbonyl, or C 1 -C 10 alkoxycarbonyl; W is - (CH 2 ) n C(=0)N(R 5a ) - ; X is - (C(R ) 2 ) n -C(R 4 ) (R 8 ) -CH(R 4 ) -, with the proviso that when n is 0 or 1, then at least one of R a or R 8 is other than H or methyl; R 5 is selected from H or C 1 -C 10 alkyl substituted with 0-6 R 4b ; R 6 is selected from H, Ci-Cio alkyl, hydroxy, Ci-Cio alkoxy, nitro, Ci-Cio alkylcarbonyl, -N(R 12 )R 13 , -NR 5 R 5a , C0 2 R 5 , S(0) m R 5 , OR 5 , cyano, halo; Cg to Cio aryl optionally substituted with 1-3 groups selected from halogen, Ci-Cg alkoxy, Ci-Cg alkyl, CF 3 , S(0)mMe, or -NMe 2 ; C 7 to Cn arylalkyl, said aryl being optionally substituted with 1-3 groups selected from halogen, Ci-Cg alkoxy, Ci-C alkyl, CF 3 , S(0)mMe, or - Me 2 ; methylenedioxy when R 6 is a substituent on aryl; or a 5-10 membered heterocyclic ring containing 1-3 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R 7 ; R 7 is selected from selected from H, C 1 -C 10 alkyl, hydroxy, C 1 -C 10 alkoxy, nitro, C 1 -C 10 alkylcarbonyl, -N(R 12 )R 13 , cyano, or halo; R 8 is selected from: -CONR 5 NR 5a ; -C0 2 R 5 ; C 1 -C 10 alkyl, substituted with 0-3 R 6 ; C 2 -C 10 alkenyl, substituted with 0-3 R 6 ; C 2 -C 10 alkynyl, substituted with 0-3 R 6 , C 3 -Cβ cycloalkyl, substituted with 0-3 R 6 ; Cs-Cg cycloalkenyl, substituted with 0-3 R 6 ; aryl, substituted with 0-2 R 6 ; 5-10 membered heterocyclic ring containing 1-3 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R 6 ; R 12 and R 13 are each independently selected from H, Ci-Cio alkyl, Ci-Cio alkoxycarbonyl, Ci-Cio alkylcarbonyl, Ci-Cio alkylsulfonyl, aryl(Cι-Cιo alkyl) sulfonyl, arylsulfonyl, aryl, heteroarylcarbonyl, or heteroarylalkylcarbonyl, wherein said aryls are optionally substituted with 0-3 substituents selected from the group consisting of: C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halo, CF 3 , and NO 2 . 8. A compound of Claim 7 wherein: Z is selected from a bond or 0; W is - (CH 2 ) n C(=0)N(R l2 ) -; X is -C(R 4 ) (R 8 ) -C(R ) 2 ". 9. A compound of Claim 7 wherein: R 1 is R 2 NHC(=NR 2 )- or R 2 NHC(=NR 2 )NH- and V is phenylene or pyridylene, or R 1 is and V is a single bond; n is 1 or 2; X is -CHR 8 CH 2 -; Y is selected from: hydroxy; Ci to Cio alkoxy; methylcarbonyloxymethoxy- ; ethylcarbonyloxymethoxy- ; t-butylcarbonyloxymethoxy- ; cyclohexylcarbonyloxymethoxy- ; 1- (methylcarbonyloxy) ethoxy- ; 1- (ethylcarbonyloxy) ethoxy- ; 1- (t-butylcarbonyloxy) ethoxy- ; 1- (cyclohexylcarbonyloxy)ethoxy- ; i-propyloxycarbonyloxymethoxy- ; t-butyloxycarbonyloxymethoxy- ; 1- (i-propyloxycarbonyloxy) ethoxy- ; 1- (cyclohexyloxycarbonyloxy) ethoxy- ; 1- (t-butyloxycarbonyloxy) ethoxy- ; dimethylaminoethoxy- ; diethylaminoethoxy- ; (5-methyl-l, 3-dioxacyclopenten-2-on-4-yl)methoxy-; (5- (t-butyl) -1, 3-dioxacyclopenten-2-on-4- yl)methoxy- ; (1,3-dioxa-5-phenyl-eyelopenten-2-on-4-yl)methoxy- ; 1- (2- (2-methoxypropyl) carbonyloxy) ethoxy- ; selected from H, Cι-C 4 alkyl, hydroxy, C 1 -C 4 alkoxy, nitro, C 1 -C 10 alkylcarbonyl, -N(R 12 )R 13 , -NR 5 R 5a , C0 2 R 5 , S(0) m R 5 , OR 5 , cyano, halo; Cg to Cio aryl optionally substituted with 1-3 groups selected from halogen, Ci-C alkoxy, Ci-C alkyl, CF 3 , S(0)mMe, or -NMe 2 ; methylenedioxy when R 6 is a substituent on aryl; or a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, triazolyl, imidazolyl, benzofuranyl, indolyl, indolinyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyridinyl, 3H- indolyl, carbazolyl, pyrrolidinyl, piperidinyl, indolinyl, isoxazolinyl or morpholinyl; R 8 is selected from: -C0NR 5 NR 5a ; -C0 2 R 5 ; i-Cio alkyl, substituted with 0-3 R 6 ; C 2 -C 10 alkenyl, substituted with 0-3 R 6 ; C 2 -C 10 alkynyl, substituted with 0-3 R 6 , C 3 -C 8 cycloalkyl, substituted with 0-3 R 6 ; aryl, substituted with 0-2 R 6 ; a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, triazolyl, imidazolyl, benzofuranyl, indolyl, indolinyl, quinolinyl, isoquinolinyl, isoxazolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyridinyl, 3H-indolyl, carbazolyl, pyrrolidinyl, piperidinyl, indolinyl, or morpholinyl, said heterocyclic ring being substituted with 0-2 R 6 ; R 12 is selected from H, Ci-C alkyl, C 1 -C 4 alkoxycarbonyl, Ci-C alkylcarbonyl, Ci-Cg alkylsulfonyl, aryl(C -C 4 alkyl) sulfonyl, arylsulfonyl, aryl, pyridylcarbonyl or pyridylmethylcarbonyl, wherein said aryls are optionally substituted with 0-3 substituents selected from the group consisting of: C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halo, CF 3 , and O 2 ; and R 13 is H. 10. A compound of Claim 6, or a pharmaceutically acceptable salt form thereof, selected from: 3 (R, S) - {5 (R, S) -N- [3- (4-amidinophenyl) isoxazolin-5- ylacetyl]amino} -3-phenylpropanoic acid; 3 (R, S) - (5 (R, S) -N- [3- ( -amidinophenyl) isoxazolin-5- ylacetyl]amino} -pentanoic acid; 3 (R) - {5 (R, S) -N- [3- (4-amidinophenyl) isoxazolin-5- ylacetyl] amino}heptanoic acid; 3 (R, S) - {5 (R, S) -N- [3- (4-amidinophenyl) isoxazolin-5- ylacetyl] amino} -4- (phenylthio)butanoic acid; 3 (R, S) - {5 (R, S) -N- [3- (4-amidinophenyl) isoxazolin-5- ylacetyl] amino} -4- (phenylsulfonamido)butanoic acid; 3 (R, S) - {5 (R, S) -N- [3- (4-amidinophenyl) isoxazolin-5- ylacetyl]amino} -4- (n-butylsulfonamido)butanoic acid; 3 (S) - {5 (R, S) -N- [3- (4-amidinophenyl) isoxazolin-5- ylacetyl]amino} -3- (adamantylmethylaminocarbonyl)propanoic acid; 3 (S) - {5 (R, S) -N- [3- (4-amidinophenyl) isoxazolin-5- ylacetyl]amino} -3- (1- azabicyclo [3.2.2]nonylcarbonyl)propanoic acid; 3 (S) - {5 (R, S) -N- [3- (4-amidinophenyl) isoxazolin-5- ylacetyl] amino} -3- (phenethylaminocarbonyl)propanoic acid. 3 (R) - {5 (R, S) -N- [3- (4-amidinophenyl) isoxazolin-5- ylacetyl]amino} -3- (3-pyridylethyl)propanoic acid. 3 (R) - {5 (R, S) -N- [3- (4-amidinophenyl) isoxazolin-5- ylacetyl]amino} -3- (2-pyridylethyl)propanoic acid. 3 (R) - {5 (R, S) -N- [3- ( -amidinophenyl) isoxazolin-5- ylacetyl]amino} -3- (phenylpropyl)propanoic acid. 11. A compound of Claim 6 of Formula Ic: (IC) wherein: b is a single or double bond; R 1 is selected from R 2a (R 3 )N-, R 2 (R 3 ) N(R 2 N=) C- , R 2a (R 3 )N(CH 2 ) q Z-, R 2 (R 3 ) N(R 2 N=) C (CH 2 ) q Z- , R 2 (R 3 )N(R 2 N=)CN(R 2 ) -, Z is selected from a bond, 0, or S; R 2 and R 3 are independently selected from H, aryl(C -Cιo alkoxy) carbonyl , or Ci-Cio alkoxycarbonyl; R 2a i s R 2 or R 2 (R3)N(R N=)C; U is a single bond, V is selected from: a single bond; - (C 1 -C 7 alkyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; - (C 2 -C 7 alkenyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; - (C 2 -C 7 alkynyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; - (phenyl) -Q- , said phenyl substituted with 0-2 groups independently selected from R 6 or R 7 ; - (pyridyl) -Q- , said pyridyl substituted with 0-2 groups independently selected from R 6 or R 7 ; or - (pyridazinyl) -Q- , said pyridazinyl substituted with 0-2 groups independently selected from R 6 or R 7 ' Q is selected from a single bond, -0-, -S(0) m -, -N(R 12 )-, -(CH 2 )m-, -C(=0)-, -N(R 5a )C(=0) -, -C(=0)N(R 5a ) -, -CH 2 0-, -0CH 2 -, -CH 2 N(R 12 )-, -N(R 12 )CH 2 -, -CH 2 C(=0)-, -C(=0)CH 2 -, -CH 2 S(0) m -, or -S(0) m CH 2 -, provided that when b is a single bond, and R 1 -U-V- is a substituent on C5 of the central 5-membered ring of Formula Ic, then Q is not -0-, -S(0) m -, -N(R 12 )-, -C(=0)N(R 5a ) -, -CH 2 0-, CH 2 N(R 12 )- or -CH 2 S(0) m -; W is selected from: - (C(R 4 ) 2 ) -C(=0) -N(R 5a ) -, or -C ( =0 ) -N ( R 5a) - ( C ( R 4 ) 2 ) -; X is -C(R 4 ) 2 -CHR 4a -; R 4 is selected from H, C -Cio alkyl, Ci-Cio alkylcarbonyl, aryl, arylalkyl, cycloalkyl, or cycloalkylalkyl; R a is selected from hydroxy, Ci-Cio alkoxy, nitro, -N(R 5 )R 5a , -N(R 12 )R 13 , or -N(R 16 )R 17 , Ci-Cio alkyl substituted with 0-3 R 6 , aryl substituted with 0-3 R 6 , or Ci-Cio alkylcarbonyl; R 4b is selected from H, C x -Cg alkyl, C 2 -Cg alkenyl, C 2 - Cg alkynyl, hydroxy, Ci-Cg alkoxy, Ci-Cg alkylthio, Ci-Cg alkylsulfinyl, Ci-C alkylsulfonyl, nitro, Ci-Cg alkylcarbonyl, Cg-Cι 0 aryl, -N(R 12 )R 13 , halo, CF 2 , CN Ci-C alkoxycarbonyl, carboxy, piperidinyl, morpholinyl or pyridyl; R 5 is selected from H or Ci-Cio alkyl substituted with 0-6 R 4b ; R 5a is selected from hydrogen, hydroxy, Ci to Cs alkyl, C 2 to Cg alkenyl, C 3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl, Ci-Cg alkoxy, benzyloxy, Cg to Cio aryl, heteroaryl, heteroarylalkyl, C 7 to Cn arylalkyl, or adamantylmethyl, C 1 -C 10 alkyl substituted with 0-2 R 4b ; alternately, R 5 and R 5a can be taken together to be 3- azabicyclononyl, 1,2,3,4-tetrahydro-1- uinolinyl, 1, 2,3, 4-tetrahydro-2-isoquinolinyl, 1-piperidinyl, 1-morpholinyl, 1-pyrrolidinyl, thiamorpholinyl, thiazolidinyl or 1-piperazinyl, each being optionally substituted with Ci-Cg alkyl, C -Cio aryl, heteroaryl, C 7 -Cn arylalkyl, Ci-C alkylcarbonyl, C 3 -C 7 cycloalkylcarbonyl, Ci-Cg alkoxycarbonyl or C 7 -C 11 arylalkoxycarbonyl; R 5b is selected from Ci-Ce alkyl, C 2 -Cg alkenyl, C 3 -C 11 cycloalkyl, C 4 -C 11 cycloalkylmethyl, Cg-Cio aryl, C 7 -C 11 arylalkyl, or C 1 -C 10 alkyl substituted with 0-2 R 4 Y is selected from hydroxy, Ci to Cio alkyloxy, C 3 to Cn cycloalkyloxy, Cg to Cio aryloxy, C 7 to Cn aralkyloxy, C 3 to Cio alkylcarbonyloxyalkyloxy, C 3 to Cio alkoxycarbonyloxyalkyloxy, C 2 to Cio alkoxycarbonylalkyloxy, C 5 to Cio cycloalkylcarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonylalkyloxy, C 7 to Cn aryloxycarbonylalkyloxy, Cβ to C 12 aryloxycarbonyloxyalkyloxy, Cβ to C 12 arylcarbonyloxyalkyloxy, C 5 to Cio alkoxyalkylcarbonyloxyalkyloxy, C 5 to Cio (5-alkyl- 1,3-dioxa-cyclopenten-2-one-yl)methyloxy, or Cio to C 14 (5-aryl-l, 3-dioxa-cyclopenten-2-one- yl)methy1oxy; R 6 and R 7 are each independently selected from H, C 1 -C 10 alkyl, hydroxy, C 1 -C 10 alkoxy, nitro, C1-C10 alkylcarbonyl, -N(R 12 )R 13 , cyano, or halo; R 12 and R 13 are each independently selected from H, C 1 -C 10 alkyl, C 1 -C 10 alkoxycarbonyl, C1-C1 0 alkylcarbonyl, C 1 -C 10 alkylsulfonyl, aryl(Cι-Cιo alkyl) sulfonyl, arylsulfonyl, heteroarylcarbonyl, heteroarylalkylcarbonyl or aryl, wherein said aryls are optionally substituted with 0-3 substituents selected from the group 3 i i consisting of: C 1 -C 4 alkyl, C 1 -C alkoxy, halo, CF 3 , and NO2; R 15 is selected from H, C 1 -C 10 alkyl, C 2 -Cιo alkenyl, C 2 -Cιo alkynyl, C 1 -C 10 alkoxy, aryl, heteroaryl or C 1 -C 10 alkoxycarbonyl, C0 2 R 5 or -C(=0)N(R 5 )R 5a ; R 16 is selected from: -C(=0) -0-R 18a , -C(=0)-R 18b , -C ( =0)N ( R 18b) 2 , -S0 2 -R 18a , or -S0 2 -N(R 18b ) 2 ; R 17 is selected from: H or C 1 -C 4 alkyl R i8a i s selected from: Ci-Cβ alkyl substituted with 0-2 R 19 , C 2 -C8 alkenyl substituted with 0-2 R 19 , C -C 8 alkynyl substituted with 0-2 R 19 , 3 -C 8 cycloalkyl substituted with 0-2 R 19 , aryl substituted with 0-4 R 19 , aryl(Cι-Cg alkyl)- substituted with 0-4 R 19 , a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, triazolyl, imidazolyl, benzofuranyl, indolyl, indolinyl, quinolinyl, isoquinolinyl, isoxazolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyrimidinyl, 3H-indolyl, carbazolyl, pyrrolidinyl, piperidinyl, indolinyl, or morpholinyl, said heterocyclic ring being substituted with 0-4 R 19 ; Ci-Cg alkyl substituted with a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolinyl, benzofuranyl, indolyl, indolenyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyridinyl, 3 H-indolyl, indolyl, carbazole, pyrrolidinyl, piperidinyl, indolinyl, or morpholinyl, said heterocyclic ring being substituted with 0-4 R 19 ; R i8b i s selected from R 18a or H; R 19 is selected from H, halogen, CF 3 , CN, N0 2 , NR 12 R 13 , Cι-C 8 alkyl, C -Cg alkenyl, C2-C6 alkynyl, Ci-Cg alkoxy, C 3 -C 11 cycloalkyl, C 4 -C 11 cycloalkylalkyl, aryl, heteroaryl, aryl(Cι-Cg alkyl)-, or C 1 -C 4 alkoxycarbonyl; n is 0-4 q is 1-7 r is 0-3, provided that n, q, and r are chosen such that the number of in-chain atoms between R 1 and Y is in the range of 8-17. 12. A compound of Claim 11 of Formula lb: ( lb) wherein: R 1 is selected from: R 2 <R 3 )N-, R NH(R 2 N=) C- , R 2 NH(R 2 N=)CNH-, R 2 R 3 N (CH 2 ) p . Z- , R 2 NH(R 2 N=)CNH(CH 2 ) "Z- or n is 0-1; p 1 is 4-6; p" is 2-4; Z is selected from a bond or 0; V is a single bond, -(phenyl)- or -(pyridyl)-; W is selected from: - (C(R 4 ) 2 ) -C(=0) -N(R 5a )-, -C(=0) -N(R 5a ) -CH 2 -; X is selected from: -CH 2 -CHN(R 16 )R 17 -, or -CH 2 -CHNR 5 R 5a -; Y is selected from: hydroxy; Ci to Cio alkoxy; methylcarbonyloxymethoxy- ethylcarbonyloxymethoxy- ; t-butylcarbonyloxymethoxy- ; eyelohexylcarbonyloxymethoxy- ; 1- (methylcarbonyloxy) ethoxy-; 1- (ethylcarbonyloxy)ethoxy- ; 1- (t-butylcarbonyloxy)ethoxy- ; 1- (cyclohexylcarbonyloxy)ethoxy- ; i-propyloxycarbonyloxymethoxy- ; t-butyloxycarbonyloxymethoxy- ; 1- (i-propyloxycarbonyloxy)ethoxy- ; 1- (cyclohexyloxycarbonyloxy)ethoxy- ; 1- (t-butyloxycarbonyloxy)ethoxy- ; dimethylaminoethoxy- ; diethylaminoethoxy-; (5-methyl-1,3-dioxacyclopenten-2-on-4-yl)methoxy- ; (5- (t-butyl) -1,3-dioxacyclopenten-2-on-4- yl)methoxy- ; (1,3- ioxa-5-phenyl-cyclopenten-2-on-4-yl)methoxy- ; 1- (2- (2-methoxypropyl)carbonyloxy) ethoxy- ; R 16 is selected from: -C(=0) -0-R 18a , -C(=0) -R 18b , -S(=0) 2 -R 18a or -S0 2 -N(R 18b ) 2 ; R 17 is selected from H or C 1 -C 5 alkyl; R i8a is selected from: Cι-C 8 alkyl substituted with 0-2 R 19 , C 2 "C 8 alkenyl substituted with 0-2 R 19 , C 2 -C 8 alkynyl substituted with 0-2 R 19 , C 3 -C 8 cycloalkyl substituted with 0-2 R 19 , aryl substituted with 0-4 R 19 , aryKCi-Cg alkyl)- substituted with 0-4 R 19 , a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, triazolyl, imidazolyl, benzo uranyl, indolyl, indolinyl, quinolinyl, isoquinolinyl, isoxazolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyrimidinyl, 3 -indolyl, carbazolyl, pyrrolidinyl, piperidinyl, indolinyl, or morpholinyl, said heterocyclic ring being substituted with 0-4 R 19 ; Ci-C alkyl substituted with a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolinyl, benzofuranyl, indolyl, indolenyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyridinyl, 3ff-indolyl, indolyl, carbazole, pyrrolidinyl, piperidinyl, indolinyl, or morpholinyl, said heterocyclic ring being substituted with 0-4 R 19 . 13. A compound of Claim 11 wherein: R 1 is R 2 NH(R 2 N=)C- or R 2 HN(R 2 N=) CNH- and V is phenylene or pyridylene, or R 1 is and V is a single bond; n is 1 or 2; i8a is selected from: C 1 - C alkyl substituted with 0 - 2 R 19 , C 2 - C 4 alkenyl substituted with 0 - 2 R 19 , C 2 -C alkynyl substituted with 0-2 R 19 , C 3 -C 7 cycloalkyl substituted with 0-2 R 19 , aryl substituted with 0-4 R 19 , ' aryl(Cι-C 4 alkyl)- substituted with 0-4 R 19 , a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, triazolyl, imidazolyl, benzofuranyl, indolyl, indolinyl, quinolinyl, isoquinolinyl, isoxazolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyrimidinyl, 3H-indolyl, carbazolyl, pyrrolidinyl, piperidinyl, indolinyl, isoxazolinyl or morpholinyl, said heterocyclic ring being substituted with 0-4 R 19 ; C 1 -C 4 alkyl substituted with a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolinyl, benzofuranyl, indolyl, indolenyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyridinyl, 3H-indolyl, indolyl, carbazole, pyrrolidinyl, piperidinyl, indolinyl, isoxazolinyl or morpholinyl, said heterocyclic ring being substituted with 0-4 R 19 . 14. A compound of Claim 6, or pharmaceutically acceptable salt forms thereof, selected from: N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (phenylsulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (4-methyl-phenyl-sulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (butanesulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (propanesulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (ethanesulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (methyloxycarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (ethyloxycarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (1-propyloxycarbonyl) -2, 3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (2-propyloxycarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (n-butyloxycarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R) -yl} - acetyl] -N2- (n-butyloxycarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2 - {3- (4-formamidinophenyl) -isoxazolin-5 (S) -yl} - acetyl] -N2- (n-butyloxycarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3 • (4-formamidinophenyl) -isoxazolin-5 (R) -yl} - acetyl] -N2- (n-butyloxycarbonyl) -2,3- (R) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 ( S) -yl} - acetyl] -N2- (n-butyloxycarbonyl) -2,3- (R) - diaminopropanoic acid; N 3 - [2 - {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (2-butyloxycarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (1- (2-methyl) -propyloxycarbonyl) -2,3- (S) -diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (2- (2-methyl) -propyloxycarbonyl) -2,3- (S) -diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (benzyloxycarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R) -yl} - acetyl] -N2- (benzyloxycarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (S) -yl} - acetyl] -N2- (benzyloxycarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (4-methylbenzyloxycarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (4-methoxybenzyloxycarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (4-chlorobenzyloxycarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (4-bromobenzyloxycarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (4-fluorobenzyloxycarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (4-phenoxybenzyloxycarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (2- (methyloxyethyl) -oxycarbonyl) -2,3- (S) -diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (2-pyridinylcarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (3-pyridinylcarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- ( -pyridinyl-carbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (2- (2-pyridinyl) -acetyl) -2, 3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (2- (3-pyridinyl) -acetyl) -2,3- (S) - diaminopropanoic acid; N 3 -[2-{3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (2- (4-pyridinyl) -acetyl) -2, 3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (2-pyridyl-methyloxycarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (3-pyridyl-methyloxycarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (4-pyridyl-methyloxycarbonyl) -2,3- (S) - diaminopropanoic acid. N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (4-butyloxyphenylsulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (2-thienylsulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (3-methylphenylsulfonyl) -2,3- (R,S) - diaminopropanoic acid; N 3 - [2 - {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (3-methylphenylsulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2 - {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (3-methylphenylsulfonyl) -2,3- (R) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R) -yl} - acetyl] -N2- (3-methylphenylsulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (S) -yl} - acetyl] -N2- (3-methylphenylsulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (S) -yl} - acetyl] -N2- (3-methylphenylsulfonyl) -2,3- (R) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R) -yl} - acetyl] -N2- (3-methylphenylsulfonyl) -2,3- (R) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (4-iodophenylsulfonyl) -2,3- (S) - diaminopropanoic acid; 2 1. N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (3-trifluoromethylphenylsulfonyl) -2,3- (S) -diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (3-chlorophenylsulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (3-2-methoxycarbonylphenylsulfonyl) -2,3- (S) -diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (2,4, 6-trimethylphenylsulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (2-chlorophenylsulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (4-trifluoromethylphenylsulfonyl) -2,3- (S) -diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (2-trifluoromethylphenylsulfonyl) -2,3- (S) -diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (2-fluorophenylsulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (4-fluorophenylsulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (4-methoxyphenylsulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2 - {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (2,3,5, 6-tetramethylphenylsulfonyl) -2,3- (S) -diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (4-cyanophenylsulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (4-chlorophenylsulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (4-propylphenylsulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (2-phenylethylsulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2 - {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (4-isopropylphenylsulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (3-phenylpropylsulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (3-pyridylsulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (phenylaminosulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (benzylaminosulfonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (dimethylaminosulfonyl) -2,3- (S) - diaminopropanoic acid, N 3 - [2- {3- (2-fluoro-4-formamidinophenyl) -isoxazolin- 5 (R, S) -yl} -acetyl] -N2- (3-methylphenylsulfonyl) -2,3- (S) -diaminopropanoic acid, N 3 - [2- {3- (2-formamidino-5-pyridinyl.) -isoxazolin-5 (R, S) - yl} -acetyl] -N2- (n-butyloxycarbonyl) -2,3- (S) - diaminopropanoic acid, N 3 - [2- {3- (2-formamidino-5-pyridinyl) -isoxazolin-5 (R, S) - yl} -acetyl] -N2- (3-methylphenylsulfonyl) -2,3- (S) - diaminopropanoic acid, N 3 - [2- {3- (3-formamidino-6-pyridinyl) -isoxazolin-5 (R, S) - yl} -acetyl] -N2- (n-butyloxycarbonyl) -2, 3- (S) - diaminopropanoic acid, N 3 - [2- {3- (3-formamidino-6-pyridinyl) -isoxazolin-5 (R, S) - yl} -acetyl] -N2- (3-methylphenylsulfonyl) -2, 3- (S) - diaminopropanoic acid, N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (phenylaminocarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (4-fluorophenylaminocarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2v {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (l-naphthylaminocarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (benzylaminocarbonyl) -2,3- (S) - diaminopropanoic acid; N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (3-bromo-2-thienylsulfonyl) -2, 3- (S) - diaminopropanoic acid; N 3 - [2- (3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (3-methyl-2-benzothienylsulfonyl) -2,3- (S) -diaminopropanoic acid, N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (isobutyloxycarbonyl) -2,3- (S) - diaminopropanoic acid, N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R) -yl} - acetyl] -N2- (isobutyloxycarbonyl) -2,3- (S) - diaminopropanoic acid, N 3 - [2 - {3- (4-formamidinophenyl) -isoxazolin-5 (S) -yl} - acetyl] -N2- (isobutyloxycarbonyl) -2,3- (S) - diaminopropanoic acid, N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (2-cyclopropylethoxycarbonyl) -2,3- (S) - diaminopropanoic acid, N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (R) -yl} - acetyl] -N2- (2-cyclopropylethoxycarbonyl) -2,3- (S) - diaminopropanoic acid, and N 3 - [2- {3- (4-formamidinophenyl) -isoxazolin-5 (S) -yl} - acetyl] -N2- (2-cyclopropylethoxycarbonyl) -2,3- (S) - diaminopropanoic acid, N 3 - [2- {3- (4-guanidinophenyl) -isoxazolin-5 (R, S) -yl} - acetyl] -N2- (n-butyloxycarbonyl) -2,3- (S) - diaminopropanoic acid. N 3 - [2- {3- (4-guanidinophenyl) -isoxazolin-5 (R) -yl} - acetyl] -N2- (n-butyloxycarbonyl) -2,3- (S) - diaminopropanoic acid. N 3 - [2- {3- (4-guanidinophenyl) -isoxazolin-5 (R) -yl} - acetyl] -N2- (3-methylphenylsulfonyl) -2,3- (S) - diaminopropanoic acid. N 3 - [2- {5- (4-formamidinophenyl) -isoxazolin-3 (R, S) -yl} - acetyl] -N2- (n-butyloxycarbonyl) -2,3- (S) - diaminopropanoic acid; 15. A prodrug ester of a compound of Claim 14, said ester being selected from the group consisting of: methyl; ethyl; isopropyl; methylcarbonyloxymethyl- ; ethylcarbonyloxymethyl- ; t-butylcarbonyloxymethy1- ; cyclohexylcarbonyloxymethyl- ; 1- (methylcarbonyloxy) ethyl- ; • 1- (ethylcarbonyloxy) ethyl- ; 1- (t-butylcarbonyloxy) ethyl- ; 1- (cyclohexylcarbonyloxy) ethyl- ; i-propyloxycarbonyloxymethyl- ; cyclohexylcarbonyloxymethyl- ; t-butyloxycarbonyloxymethyl- ; 1- (i-propyloxycarbonyloxy) ethyl- ; 1- (cyclohexyloxycarbonyloxy) ethyl- ; 1- (t-butyloxycarbonyloxy) ethyl- ; dimethylaminoethyl- ; diethylaminoethyl- ; (5-methyl-l, 3-dioxacyclopenten-2-on-4-yl)methyl- ; (5- (t-butyl) -1, 3-dioxacyclopenten-2-on- 4-yl)methyl- ; (1,3-dioxa-5-phenyl-eyelopente -2-on-4-yl)methyl- ; 1- (2- (2-methoxypropyl) carbonyloxy) ethyl- . 16. A compound of Formula Id: or a pharmaceutically acceptable salt form thereof wherein: R 1 is selected from is selected from R 2 (R 3 )N-, R 2 (R 3 )N(R 2 N=)C-, R (R 3 )N(R 2 N=)CN(R 2 ) -, R 2 (R 3 )N(CH 2 ) q Z-, R 2 (R 3 )N(R N=) C(CH 2 ) g Z- , R (R 3 )N(R 2 N=)CN(R 2 ) (CH ) q Z-, piperazinyl- (CH 2 ) q Z- or Z is selected from a bond, 0, S, S(=0), or S(=0) 2 ; R 2 and R 3 are independently selected from: H, Ci-Cio alkyl, C 2 -Cg alkenyl, C 3 -C 11 cycloalkyl, C -Cn cycloalkylalkyl, C 6 -Cι 0 aryl, C 7 -C ar y lalk y l , C 2 -C 7 alkylcarbonyl, C 7 -Cn arylcarbonyl, C 2 -Cιo alkoxycarbonyl, C 4 -Cn cycloalkoxycarbonyl, C 7 -Cn bicycloalkoxycarbonyl, C 7 -C 11 aryloxycarbonyl , or aryl (Ci- Cio alkoxy) carbonyl , Ci-Cg alkylcarbonyloxy (C 1 -C 4 alkoxy) carbonyl , Cg-Cio arylcarbonyloxy (C 1 -C 4 alkoxy) carbonyl , C 4 -Cn cycloalkylcarbonyloxy ( Ci - C 4 alkoxy) carbonyl ; U is selected from: a single bond, C 1 -C 7 alkylene, C 2 -C 7 alkenylene, C 2 -C 7 alkynylene, arylene substituted with 0-3 R 6a , , or pyridylene substituted with 0-3 R 6a ; V is selected from: a single bond; C 1 -C 7 alkylene substituted with 0-6 R 6 or R 7 ; C 2 -C 7 alkenylene substituted with 0-4 R 6 or R 7 ; C 2 -C 7 alkynylene substituted with 0-4 R 6 or R 7 ; phenylene substituted with 0-4 R 6 or R 7 ; pyridylene substituted with 0-3 R 6 or R 7 ; pyridazinylene substituted with 0-3 R 6 or R 7 ; X is selected from: a single bond; - (CH 2 ) n C(=0)N(R 12 ) -; C 1 -C 7 alkylene substituted with 0-6 R 4 , R 8 or R 15 ; C 2 -C 7 alkenylene substituted with 0-4 R 4 , R 8 or R 15 ; C 2 -C 7 alkynylene substituted with 0-4 R 4 , R 8 or R 15 ; Y is selected from: hydroxy, Ci to Cio alkyloxy, C 3 to Cn cycloalkyloxy, Cg to Cio aryloxy, C 7 to Cn aralkyloxy, C 3 to C o alkylcarbonyloxyalkyloxy, C 3 to Cio alkoxycarbonyloxyalkyloxy, C to Cio alkoxycarbonylalkyloxy, C 5 to Cio cycloalkylcarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonylalkyloxy, C 7 to Cn aryloxycarbonylalkyloxy, Cβ to Cι 2 aryloxycarbonyloxyalkyloxy, Cβ to Cι 2 arylcarbonyloxyalkyloxy, C 5 to C o alkoxyalkylcarbonyloxyalkyloxy, C 5 to Cio (5-alkyl-1, 3-dioxa-cyclopenten-2-one- yDmethyloxy, Cio to c i 4 (5-aryl-l, 3-dioxa-cyclopenten-2-one- yl)methyloxy; (R 2 ) (R 3 )N- (C 1 -C 10 alkoxy) -; R 14 and W are attached to the same carbon and taken together to form a spiro-fused, 5-7 membered ring structure of the formula: D, E, F and G are each independently selected from: C(R 6a ) 2 ; carbonyl; a heteroatom moiety selected from N, N(R 12 ) , 0, provided that no more than 2 of D, E, F and G are N, N(R 12 ) , 0, S, or C(=0); alternatively, the bond between D and E, E and F, or F and G in such spiro-fused ring may be a carbon-nitrogen double bond or a carbon-carbon double bond; R 4 is selected from H, Ci-Cio alkyl, hydroxy, Ci-Cio alkoxy, nitro, Ci-Cio alkylcarbonyl, or -N(R 12 )R 13 ; R 6 and R 7 are each independently selected from H, Ci-Cio alkyl, hydroxy, Ci-Cio alkoxy, nitro, Ci-Cio alkylcarbonyl, -N(R 12 )R 13 , cyano, halo, CF 3 , CHO, C0 2 R 5a , C(=0)R 5a , CONHR 5a , C0N(R 12 ) 2 , OC(=0)R 5a , 0C(=0)0R 5a , 0R 5a , 0C(=0)N(R 1 ) 2 , 0CH 2 C0 2 R 5a , C0 2 CH 2 C0 2 R 5a , N(R 12 ) 2 , N0 2 , NR 12 C(=0)R 5a , NR 12 C(=0)0R 5a , NR 1 C(=0)N(R 12 ) , NR 12 S0 2 N(R 12 ) 2 , NR 12 S0 R 5a , S(0) p R 5a , S0 N(R 12 ) 2 , C 2 to Cg alkenyl, C 3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl; Cg to Cio aryl optionally substituted with 1-3 groups selected from halogen, Ci-Cg alkoxy, Ci-Cε alkyl, CF 3 , S(0)m e, or -NMe 2 ; C 7 to Cn arylalkyl, said aryl being optionally substituted with 1-3 groups selected from halogen, Ci-Cg alkoxy, Ci-Cg alkyl, CF 3 , S(0)mMe, or -NMe 2 ; methylenedioxy when R 6 is a substituent on aryl; R 6a is selected from C 1 -C alkyl, C 1 -C 4 alkoxy, halo, CF 3 , N0 2 , or NR 12 R 13 ; R 8 is selected from: H; R 6 ; C 1 -C 10 alkyl, substituted with 0-8 R 6 ; C 2 -Cιo alkenyl, substituted with 0-6 R 6 ; C 2 -Cιo alkynyl, substituted with 0-6 R 6 ; C 3 -C 8 cycloalkyl, substituted with 0-6 R 6 ; Cs-Cg cycloalkenyl, substituted with 0-5 R 6 ; aryl, substituted with 0-5 R 6 ; 5-6 membered heterocyclic ring containing 1-2 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-5 R 6 ; R 12 and R 13 are independently H, C 1 -C 10 alkyl, C 1 -C 10 alkoxycarbonyl, C 1 -C 10 alkylcarbonyl, C 1 -C 10 alkylsulfonyl, aryl(Cι-Cιo alkyl) sulfonyl, arylsulfonyl, aryl, C 2 -Cg alkenyl, C 3 -C 11 cycloalkyl, C 4 -C 11 cycloalkylalkyl, C 7 -C 11 ary l a lk y l , C 2 -C 7 alkylcarbonyl, C 7 -Cn arylcarbonyl, C 2 -C 10 alkoxycarbonyl, C 4 -Cn cycloalkoxycarbonyl, C 7 -C 11 bicycloalkoxycarbonyl, C 7 -C 11 aryloxycarbonyl, heteroarylcarbonyl, heteroarylalkylcarbonyl or aryl (Ci-Cio alkoxy) carbonyl, wherein said aryls or heteroaryls are optionally substituted with 0-3 substituents selected from the group consisting of: C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halo, CF 3 , and N0 2 ; R 5 and R 5a are selected independently from H, Ci to C 8 alkyl, C 2 to Cg alkenyl, C 3 to Cn cycloalkyl, C to Cn cycloalkylmethyl, Cg to Cι 0 aryl, C 7 to Cn arylalkyl, or C 1 -C 10 alkyl substituted with 0-8 R 4 ; R 15 is selected from: H; R 6 ; C 1 -C 10 alkyl, substituted with 0-8 R 6 ; C 2 -Cιo alkenyl, substituted with 0-6 R 6 ; C 1 -C 10 alkoxy, substituted with 0-6 R 6 ; aryl, substituted with 0-5 R 6 ; 5-6 membered heterocyclic ring containing 1-2 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-5 R 6 ; C1-C10 alkoxycarbonyl substituted with 0-8 R 6 ; C0 2 R 5 ; or -C(=0)N(R 12 )R 13 ; n is 0-4 p is 1-3 q is 1-7 r is 0-3 provided that n, p, q and r are chosen such that the number of atoms between R 1 and Y is in the range of 8-17. 17. A compound of Claim 16 of Formula III: wherein: R 1 is selected from R 2 HN- , H 2 N(R 2 N=)C-, H 2 N(R 2 N=) CNH- , R 2 HN(CH 2 )q0-, H 2 N(R 2 N=) CNH(CH 2 )qO- , piperazinyl- (CH 2 ) q O-, R 2 is selected from H, aryl(Cι-Cιo alkoxy) carbonyl, or Ci-Cio alkoxycarbonyl; R 4 is selected from H, Ci-Cio alkyl, hydroxy, Ci-Cio alkoxy, nitro, Ci-Cio alkylcarbonyl, or -N(R 12 )R 13 ; V is selected from: a single bond; C 1 -C 7 alkylene substituted with 0-6 R 6 or R 7 ; C 2 -C 7 alkenylene substituted with 0-4 R 6 or R 7 ; 2 -C 7 alkynylene substituted with 0-4 R 6 or R 7 ; phenylene substituted with 0-3 R 6 or R 7 ; pyridylene substituted with 0-3 R 6 or R 7 ; pyridazinylene substituted with 0-3 R 6 or R 7 ; X is selected from - (CH 2 ) n C (=0)N(R 12 ) - , C 1 -C 7 alkylene substituted with 0-1 R 4 , C 2 -C 7 alkenylene, or C 2 -C 7 alkynylene; Y is selected from: hydroxy, Ci to Cio alkyloxy, C3 to Cn cycloalkyloxy, Cβ to Cio aryloxy, C 7 to Cn aralkyloxy, C3 to Cio alkylcarbonyloxyalkyloxy, C3 to Cio alkoxycarbonyloxyalkyloxy, C2 to Cio alkoxycarbonylalkyloxy, C 5 to Cio cycloalkylcarbonyloxyalkyloxy, C5 to Cio cycloalkoxycarbonyloxyalkyloxy, C5 to Cio cycloalkoxycarbonylalkyloxy, C 7 to Cn aryloxycarbonylalkyloxy, C8 to C12 aryloxycarbonyloxyalkyloxy, C8 to C12 arylcarbonyloxyalkyloxy, C5 to Cio alkoxyalkylcarbonyloxyalkyloxy, C5 to Cio (5-alkyl-l,3-dioxa-cyclopenten-2-one- yDmethyloxy, or Cio to C 14 (5-aryl-l,3-dioxa-cyclopenten-2-one- yl)methyloxy; is selected from 0 or CH 2 ; D, E, F and G are each independently selected from: CH 2 ; carbonyl; a heteroatom moiety selected from N, NH, 0, provided that no more than 2 of D, E, F and G are N, NH, 0 or S; alternatively, the bond between D and E, E and F, or F and G in such spiro-fused ring may be a carbon-nitrogen double bond or a carbon-carbon double bond; R 6 and R 7 are each independently selected from H, C 1 -C 10 alkyl, hydroxy, C 1 -C 10 alkoxy, nitro, C 1 -C 10 alkylcarbonyl, -N(R 1 )R 13 , cyano, or halo; R 12 and R 13 are each independently selected from H, Ci-Cio alkyl, Ci-Cio alkoxycarbonyl, Cι-Cι 0 alkylcarbonyl, Ci-Cio alkylsulfonyl, aryl(Cι-Cιo alkyl) sulfonyl, arylsulfonyl, heteroarylcarbonyl, heteroaryalkylcarbonyl or aryl; n is 0-4 p is 1-3 q is 1-7 r is 0-3, provided that n, p, q and r are chosen such that the number of atoms between R 1 and Y is in the range of 8-17. 18. A compound of Claim 17 wherein: R 1 is R 2 NHC(=NR 2 )- and V is phenyl or pyridyl or R 1 is and V is a single bond; n is 1 or 2; X is C 1 -C 4 alkylene substituted with 0-1 R 4 ; Y is selected from: hydroxy; Ci to Cio alkoxy; methylcarbonyloxymethoxy- ; ethylcarbonyloxymethoxy- ; t-butylcarbonyloxymethoxy- ; cyclohexylcarbonyloxymethoxy- ; 1- (methylcarbonyloxy) ethoxy- ; 1- (ethylcarbonyloxy)ethoxy- ; 1- (t-butylcarbonyloxy) ethoxy- ;' 1- (cyclohexylcarbonyloxy) ethoxy- ; i- ropyloxycarbonyloxymethoxy- ; £-butyloxycarbonyloxymethoxy- ; 1- (i-propyloxycarbonyloxy) ethoxy- ; 1- (cyclohexyloxycarbonyloxy) ethoxy- ; 1- ( -butyloxycarbonyloxy) ethoxy- ; dimethylaminoethoxy- ; diethylaminoethoxy- ; (5-methyl-1,3- ioxacyclopenten-2-on-4-yl)methoxy- ; (5- (t-butyl) -1,3-dioxacyclopenten-2-on-4- yl)methoxy- ; (1,3-dioxa-5-phenyl-cyclopenten-2-on-4-yl)methoxy- ; 1- (2- (2-methoxypropyl) carbonyloxy) ethoxy- ; R 12 and R 13 are each independently selected from H, Ci-Cg alkyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkylsulfonyl, aryl(Cι-C alkyl) sulfonyl, arylsulfonyl, heteroarylcarbonyl, heteroaryalkylcarbonyl or aryl; and R 13 is H. 19. A compound of Claim 16, or pharmaceutically acceptable salt forms thereof, selected from: 5 (R, S) -3- (4-amidinophenyl) -8- (2-carboxyethyl) -l-oxa-2, 8- diazaspiro [4.4]non-2-ene-7,9-dione; 5 (R, S) -3- (4-amidinophenyl) -8- (3-carboxypropyl) -1-oxa- 2, 8-diazaspiro [4.4]non-2-ene-7, 9-dione; 5 (R, S) -3- (4-amidinophenyl) -8- (2-carboxyethyl) -l-oxa-2, 8- diazaspiro [ .4]non-2-ene-5-one; 5 (R, S) -3- (4-amidinophenyl) -8- (3-carboxypropyl) -l-oxa- 2, 8-diazaspiro [4.4]non-2-ene-5-one; 5 (R, S) -3- (4-amidinophenyl) -8- (2-carboxyethyl) -l-oxa-2- azaspiro [4.4]nona-2, 8-diene-5-one; 5 (R, S) -3- (4-amidinophenyl) -8- (3-carboxypropyl) -l-oxa-2- azaspiro [4.4]nona-2, 8-diene-5-one; 5 (R, S) -3- (4-amidinophenyl) -8- (2-carboxyethyl) -l-oxa-2, 8- diazaspiro [4.4] dec-2-ene-7, 9-dione; 5 (R, S) -3- (4-amidinophenyl) -8- (3-carboxypropyl) -1-oxa- 2, 8-diazaspiro [4.4] dec-2-ene-7 , 9-dione; 5 (R, S) -3- (4-amidinophenyl) -8- (2-carboxyethyl) -l-oxa-2, 8- diazaspiro [4.4] dec-2-ene-5-one; 5 (R, S) -3- (4-amidinophenyl) -8- (3-carboxypropyl) -1-oxa- 2,8- iazaspiro [4.4]dec-2-ene-5-one; 5 (R, S) -3- (4-amidinophenyl) -8- (2-carboxyethyl) -l-oxa-2- azaspiro [4.4] eca-2, 8-diene-5-one; 5 (R, S) -3- (4-amidinophenyl) -8- (3-carboxypropyl) -l-oxa-2- azaspiro [4.4] deca-2, 8-diene-5-one; 5 (R, S) -3- (4-amidinophenyl) -8- (2-carboxyethyl) -l-oxa-2, 8- diazaspiro [4.4]undec-2-ene-7, 9-dione; 5 (R, S) -3- (4-amidinophenyl) -8- (3-carboxypropyl) -1-oxa- 2, 8-diazaspiro [ . ]undec-2-ene-7, 9-dione; 5 (R, S) -3- (4-amidinophenyl) -8- (2-carboxyethyl) -l-oxa-2, 8- diazaspiro [4.4]undec-2-ene-5-one; 5 (R, S) -3- (4-amidinophenyl) -8- (3-carboxypropyl) -1-oxa- 2, 8-diazaspiro [4.4]undec-2-ene-5-one; 5 (R, S) -3- (4-amidinophenyl) -8- (2-carboxyethyl) -l-oxa-2- azaspiro [4.4]undeca-2, 8-diene-5-one; 5 (R, S) -3- (4-amidinophenyl) -8- (3-carboxypropyl) -l-oxa-2- azaspiro [4.4]undeca-2, 8-diene-5-one; 5 (R, S) -3- [2- (piperidin- -yl) ethyl] -8- (2-carboxyethyl) -1- oxa-2, 8-diazaspiro [4.4] non-2-ene-7 , 9-dione; 5 (R, S) -3- [2- (piperidin-4-yl) ethyl] -8- (3-carboxypropyl) - l-oxa-2, 8-diazaspiro [4.4] on-2-ene-7 , 9-dione; 5 (R, S) -3- [2- (piperidin-4-yl) ethyl] -8- (2-carboxyethyl) -1- oxa-2, 8-diazaspiro [4.4]non-2-ene-5-one; 5 (R, S) -3- [2- (piperidin-4-yl)ethyl] -8- (3-carboxypropyl) - l-oxa-2, 8-diazaspiro [4.4]non-2-ene-5-one; 5 (R, S) -3- [2- (piperidin-4-yl)ethyl] -8- (2-carboxyethyl) -1- oxa-2-azaspiro [4.4]nona-2, 8-diene-5-one; 5 (R, S) -3- [2- (piperidin-4-yl) ethyl] -8- (3-carboxypropyl) - 1-oxa-2-azaspiro [4.4]nona-2, 8-diene-5-one; 5 (R, S) -3- [2- (piperidin- -yl) ethyl] -8- (2-carboxyethyl) -1- oxa-2, 8-diazaspiro [4.4] dec-2-ene-7 , 9-dione; 5 (R, S) -3- [2- (piperidin-4-yl) ethyl] -8- (3-carboxypropyl) - l-oxa-2, 8-diazaspiro [4.4] dec-2-ene-5,7-dione; 5 (R, S) -3- [2- (piperidin-4-yl) ethyl] -8- (2-carboxyethyl) -1- oxa-2,8-diazaspiro [4.4] dec-2-ene-5-one; 5 (R, S) -3- [2- (piperidin-4-yl)ethyl] -8- (3-carboxypropyl) - l-oxa-2, 8-diazaspiro [4.4]dec-2-ene-5-one; 5 (R, S) -3- [2- (piperidin-4-yl)ethyl] -8- (2-carboxyethyl) -l- oxa-2-azaspiro[4.4]deca-2, 8-diene-5-one; 5 (R, S) -3- [2- (piperidin-4-yl) ethyl] -8- (3-carboxypropyl) - 1-oxa-2-azaspiro [4.4]deca-2, 8-diene-5-one; 5 (R, S) -3- [2- (piperidin-4-yl) ethyl] -8- (2-carboxyethyl) -1- oxa-2,8-diazaspiro[4.4]undec-2-ene-7 ,9-dione; 5 (R, S) -3- [2- (piperidin-4-yl) ethyl] -8- (3-carboxypropyl) - l-oxa-2,8-diazaspiro[4.4]undec-2-ene-7,9-dione; 5 (R, S) -3- [2- (piperidin-4-yl) ethyl] -8- (2-carboxyethyl) -1- oxa-2,8-diazaspiro[4.4]undec-2-ene-5-one; 5 (R, S) -3- [2- (piperidin-4-yl)ethyl] -8- (3-carboxypropyl) - l-oxa-2,8-diazaspiro[4.4]undec-2-ene-5-one; 5 (R, S) -3- [2- (piperidin-4-yl)ethyl] -8- (2-carboxyethyl) -1- oxa-2-azaspiro [4.4]undeca-2, 8-diene-5-one; 5 (R, S) -3- [2- (piperidin-4-yl)ethyl] -8- (3-carboxypropyl) - 1-oxa-2-azaspiro [4.4]undeca-2, 8-diene-5-one; 5 (R,S) -3- (4-amidinophenyl) -8- [2- (benzyloxycarbonylamino) -2-carboxyethyl] -1-oxa- 2, 8-diazaspiro [4.5]dec-2-ene. 20. A compound of Formula I: or pharmaceutically acceptable salt form thereof, wherein: R 1 is selected from: R (R 3 )N(CH 2 ) q Z-, R 2 (R 3 )N(R N=) C(CH 2 ) q Z- , R 2 (R 3 )N(R N=)CN(R 2 ) (CH 2 ) q Z-, piperazinyl- (CH ) q Z- or Z is selected from 0, S, S (=0) , S(=0) 2 ; R 2 and R 3 are independently selected from: H, Ci-Cio alkyl, C -Cg alkenyl, C 3 -C 11 cycloalkyl, C 4 -C 11 cycloalkylalkyl, Cg-Cio aryl, C 7 -C u ary l a lk y l , C 2 -C 7 alkylcarbonyl, C7-C 11 arylcarbonyl, C 2 -Cιo alkoxycarbonyl, C 4 -C 11 cycloalkoxycarbonyl, C 7 -C 11 bicycloalkoxycarbonyl, C 7 -C 11 aryloxycarbonyl, or aryl (Ci-Cio alkoxy)carbonyl, Ci-Cg alkylcarbonyloxy(C 1 -C 4 alkoxy)carbonyl, Cg-Cio arylcarbonyloxy(C 1 -C 4 alkoxy) carbonyl, C 4 -C 11 cycloalkylcarbonyloxy(Ci-C 4 alkoxy) carbonyl; U is optionally present and is selected from C 1 -C7 alkylene, C 2 -C 7 alkenylene, C -C 7 alkynylene, arylene, or pyridylene; V is selected from: a single bond; C 1 -C 7 alkylene substituted with 0-6 R 6 or R 7 ; C 2 -C 7 alkenylene substituted with 0-4 R 6 or R 7 ; C 2 -C 7 alkynylene substituted with 0-4 R 6 or R 7 ; phenylene substituted with 0-4 R 6 or R 7 ; pyridylene substituted with 0-3 R 6 or R 7 ; pyridazinylene substituted with 0-3 R 6 or R 7 ; W is -(aryl)-Z 1 -, wherein said aryl is substituted with 0-6 R 6 or R 7 ; Z 1 is selected from a single bond, -CH -, 0 or S; X is selected from: a single bond; C 1 -C 7 alkylene substituted with 0-6 R 4 , R 8 or R 15 ; C 2 -C 7 alkenylene substituted with 0-4 R 4 , R 8 or R 15 ; C 2 -C 7 alkynylene substituted with 0-4 R 4 , R 8 or R 15 ; Y is selected from hydroxy, Ci to Cio alkyloxy, C 3 to Cn cycloalkyloxy, Cg to Cio aryloxy, C 7 to Cn aralkyloxy, C 3 to Cio alkylcarbonyloxyalkyloxy, C 3 to Cio alkoxycarbonyloxyalkyloxy, C 2 to Cio alkoxycarbonylalkyloxy, C 5 to Cio cycloalkylcarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonylalkyloxy, C 7 to Cn aryloxycarbonylalkyloxy, Cs to Cι aryloxycarbonyloxyalkyloxy, Cβ to Cι 2 arylcarbonyloxyalkyloxy, C 5 to Cio alkoxyalkylcarbonyloxyalkyloxy, C 5 to Cio (5-alkyl- 1, 3-dioxa-cyclopenten-2-one-yDmethyloxy, Cio to C 14 (5-aryl-1,3- ioxa-cyclopenten-2-one-yl)methyloxy; (R 2 ) (R 3 )N- (C 1 -C 10 alkoxy)-; R 4 is selected from H, Ci-Cio alkyl, hydroxy, Ci-Cio alkoxy, nitro, Ci-Cio alkylcarbonyl, or -N(R 12 )R 13 ; R 6 and R 7 are each independently selected from H, Ci-Cio alkyl, hydroxy, Ci-Cio alkoxy, nitro, Ci-Cio alkylcarbonyl, -N(R 12 )R 13 , cyano, halo, CF 3 , CHO, C0 2 R 5a , C(=0)R 5a , CONHR 5a , CON(R 12 ) 2 , OC(=0)R 5a , OC(=0)OR 5a , 0R 5a , 0C(=0)N(R 12 ) 2 , OCH C0 2 R 5a , C02CH 2 C0 2 R 5a , N(R 12 ) 2 , N0 2 , NR 12 C(=0)R 5a , NR 12 C(=0)0R 5a , NR 12 C(=0)N(R 12 ) 2 , NR 12 S0 2 N(R 12 ) 2 , NR 12 S0 R 5a , S(0) p R 5a , S0 2 N(R 12 ) 2 , C 2 to Cg alkenyl, C 3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl; Cg to Cio aryl optionally substituted with halogen, alkoxy, alkyl, -CF 3 , S(0)mMe, or -NMe 2 ; or C7 to Cn arylalkyl said aryl being optionally substituted with halogen, alkoxy, alkyl, -CF 3 , S(0)m e, or -NMe 2 ; R 8 is selected from: H; R 6 ; C 1 -C 10 alkyl, substituted with 0-8 R 6 ; C 2 -Cιo alkenyl, substituted with 0-6 R 6 ; C 2 -C 10 alkynyl, substituted with 0-6 R 6 ; 3 -C 8 cycloalkyl, substituted with 0-6 R 6 ; C 5 -Cg cycloalkenyl, substituted with 0-5 R 6 ; aryl, substituted with 0-5 R 6 ; 5-6 membered heterocyclic ring containing 1-2 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-5 R 6 ; R 12 and R 13 are independently H, Ci-Cio alkyl, Ci-Cio alkoxycarbonyl, Ci-Cio alkylcarbonyl, Ci-Cio alkylsulfonyl, aryl(Cι-Cιo alkyl) sulfonyl, arylsulfonyl, aryl, C 2 -Cg alkenyl, C 3 -C 11 cycloalkyl, C 4 -C cycloalkylalkyl, C 7 -Cn ary l a lk y l , C 2 -C 7 alkylcarbonyl, C7-C 11 arylcarbonyl, C 2 -Cιo alkoxycarbonyl, C 4 -C 11 cycloalkoxycarbonyl, C 7 -C 11 bicycloalkoxycarbonyl, C 7 -Cn aryloxycarbonyl, heteroarylcarbonyl, heteroarylalkylcarbonyl or aryl (Ci-Cio alkoxy)carbonyl; R 14 is selected from H, C1-C 10 alkyl, C 2 -Cιo alkenyl, C -C 10 alkynyl, C 1 -C 10 alkoxy, aryl, heteroaryl or C 1 -C1 0 alkoxycarbonyl, C0 2 R 5 or -C(=0)N(R 12 )R 13 ; R 5 and R 5a are selected independently from H, Ci to Cβ alkyl, C 2 to Cg alkenyl, C 3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl, Cg to Cio aryl, C 7 to Cn arylalkyl, or C 1 -C 10 alkyl substituted with 0-8 R 4 ; R 15 is selected from: H; R 6 ; C 1 -C 10 alkyl, substituted with 0-8 R 6 ; C 2 -Cιo alkenyl, substituted with 0-6 R 6 ; C 1 -C 10 alkoxy, substituted with 0-6 R 6 ; aryl, substituted with 0-5 R 6 ; 5-6 membered heterocyclic ring containing 1-2 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-5 R 6 ; C 1 -C 10 alkoxycarbonyl substituted with 0-8 R 6 ; C0 2 R 5 ; or -C(=0)N(R 12 )R 13 ; \ 4 n is 0 -4 q is 2 - 7 r is 0 - 3 provided that n, q, and r are chosen such that the number of atoms between R 1 and Y is about 8-17 21. A compound of Claim 20 of Formula IV: wherein: R 1 is selected from R 2 H (CH 2 ) q 0- , R 2 HN(R N=C)NH(CH 2 ) q 0-, piperazinyl- (CH 2 ) q 0- , or Z is 0; R 2 is selected from H, aryl(Ci-Cio)alkoxycarbonyl, Ci-Cio alkoxycarbonyl; V is selected from: a single bond; C 1 -C 7 alkylene substituted with 0-6 R 6 or R 7 ; C 2 -C 7 alkenylene substituted with 0-4 R 6 or R 7 ; C 2 -C 7 alkynylene substituted with 0-4 R 6 or R 7 ; phenylene substituted with 0-3 R 6 or R 7 ; pyridylene substituted with 0-3 R 6 or R 7 ; pyridazinylene substituted with 0-3 R 6 or R 7 ; Z 1 is selected from a single bond, 0 or S; X is selected from: a single bond; C 1 -C 7 alkylene substituted with 0-4 R 4 , R 8 or R 15 ; C 2 -C 7 alkenylene substituted with 0-3 R 4 , R 8 or R 15 ; C 2 -C 7 alkynylene substituted with 0-3 R 4 , R 8 or R 15 ; Y selected from hydroxy, Ci to Cio alkyloxy, C 3 to Cn cycloalkyloxy, Cg to Cio aryloxy, C 7 to Cn aralkyloxy, C 3 to Cio alkylcarbonyloxyalkyloxy, C 3 to Cio alkoxycarbonyloxyalkyloxy, C 2 to Cio alkoxycarbonylalkyloxy, C 5 to Cio cycloalkylcarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonylalkyloxy, C 7 to Cn aryloxycarbonylalkyloxy, Cβ to Cι 2 aryloxycarbonyloxyalkyloxy, Cβ to C i2 arylcarbonyloxyalkyloxy, C 5 to Cio alkoxyalkylcarbonyloxyalkyloxy, C 5 to Cio (5-alkyl- l,3-dioxa-cyclopenten-2-one-yl)methyloxy, or Cio to C 14 (5-aryl-1,3-dioxa-cyclopenten-2-one- yl)methyloxy; R 4 is selected from H, Cι-Cι 0 alkyl, hydroxy, Cι-Cι 0 alkoxy, nitro, C 1 -C 10 alkylcarbonyl, or -N(R 12 )R 13 ; R 6 and R 7 are selected from H, C 1 -C 10 alkyl, hydroxy, C 1 -C 10 alkoxy, nitro, C 1 -C 0 alkylcarbonyl, -N(R 12 )R 13 , cyano, or halo; R 8 is selected from H, C 1 -C 10 alkyl, C 2 -Cιo alkenyl, C 3 -C 8 cycloalkyl, Cs-Cg cycloalkenyl, aryl, 5-6 membered heterocyclic ring containing 1-2 N, 0, or S, where said heterocyclic ring may be saturated, partially saturated, or fully unsaturated; R 12 and R 13 are independently selected from H, Ci-Cio alkyl, Ci-Cio alkoxycarbonyl, Ci-Cio alkylcarbonyl, Ci-Cio alkylsulfonyl, aryl(Cι-Cιo alkyl) sulfonyl, arylsulfonyl, heteroarylcarbonyl, heteroarylalkylcarbonyl or aryl; R 14 is selected from H, Ci-Cio alkyl, C 2 -Cιo alkenyl, C 2 -Cιo alkynyl, Ci-Cio alkoxy, aryl, heteroaryl or Ci-Cio alkoxycarbonyl, C0 R 5 or -C(=0)N(R 12 )R 13 ; R 5 is selected from H or Ci-Cio alkyl substituted with 0-6 R 4 ; n is 0-4; q is 2-7; provided that n and q are chosen such that the number of atoms between R 1 and Y is in the range of 8-17. 22. A compound of Claim 21 wherein: R 1 is R 2 HN(CH 2 )q0- or V is C 1 -C 3 alkylene; Z 1 is a single bond or 0; X is C 1 -C 3 alkylene substituted with 0-1 R 4 ; Y is selected from: hydroxy; Ci to Cio alkoxy; methylcarbonyloxymethoxy- ; ethylcarbonyloxymethoxy- ; t-butylcarbonyloxymethoxy- ; cyclohexylcarbonyloxymethoxy- ; 1- (methylcarbonyloxy)ethoxy- ; 1- (ethylcarbonyloxy)ethoxy- ; 1- (t-butylcarbonyloxy) ethoxy- ; 1- (cyclohexylcarbonyloxy) ethoxy- ; i-propyloxycarbonyloxymethoxy- ; t-butyloxycarbonyloxymethoxy- ; 1- (i-propyloxycarbonyloxy)ethoxy- ; 1- (cyclohexyloxycarbonyloxy) ethoxy- ; 1- ( -butyloxycarbonyloxy)ethoxy- ; dimethylaminoethoxy- ; diethylaminoethoxy- ; (5-methyl-1,3-dioxacyclopenten-2-on-4-yl) ethoxy- ; (5- ( -butyl) -1,3-dioxacyclopenten-2-on-4- yl)methoxy- ; (1,3-dioxa-5-phenyl-eyelopenten-2-on-4-yl)methoxy-; 1- (2- (2-methoxypropyl) carbonyloxy)ethoxy- ; R 12 and R 13 are independently selected from H, Ci-Cg alkyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyl, Ci-Cg alkylsulfonyl, aryl(Cι-C 4 alkyl) sulfonyl, arylsulfonyl, heteroarylcarbonyl, heteroarylalkylcarbonyl or aryl; R 13 is H. 23. A compound of Claim 20, or a pharmaceutically acceptable salt form thereof, selected from: 5 (R, S) -4- [3- (piperidin-4-yl)oxymethylisoxazolin-5-yl]hy- drocinnamic acid; 5 (R, S) -4- [3- (2-aminoethoxymethyl)isoxazolin-5-yl]hydro- cinnamic acid; 5 (R, S) -4- [3- (3-aminopropyloxymethyl) isoxazolin-5-yl]hy- drocinnamic acid; 5 (R,S) -4- [3- (piperidin-4-yl)oxymethylisoxazolin-5- yl]phenoxyacetic acid; 5 (R,S) -4- [3- (2-aminoethoxymethyl) isoxazolin-5-yl]phen¬ oxyacetic acid; 5(R,S) -4- [3- (3-aminopropyloxymethyl) isoxazolin-5- yl]phenoxyacetic acid. 24. A compound of Formula I: or a pharmaceutically acceptable salt form thereof wherein: b is a single or double bond; R 1 is selected from R a (R 3 )N-, R 2 (R 3 )N(R 2 N=) C- , R 2a (R 3 )N(CH 2 ) q Z-, R 2 (R 3 )N(R 2 N=) C(CH 2 ) q Z- , Z is selected from a bond, 0, S, S(=0), S(=0) ; R 2 and R 3 are independently selected from: H, Ci-C o alkyl, C 2 -Cg alkenyl, C 3 -C 11 cycloalkyl, C 4 -Cn cycloalkylalkyl, Cg-Cι 0 aryl, C 7 -C n ary l alky l , C 2 -C 7 alkylcarbonyl, C 7 -C 11 arylcarbonyl, C 2 -Cιo alkoxycarbonyl, C 4 -C 11 cycloalkoxycarbonyl, C 7 -C 11 bicycloalkoxycarbonyl, C 7 -C 11 aryloxycarbonyl, aryl (Ci-Cio alkoxy) carbonyl, alkylcarbonyloxyalkoxycarbonyl, or alkoxycarbonyloxyalkoxycarbonyl, Ci-Cg alkylcarbonyloxy(Ci-C 4 alkoxy) carbonyl, Cg-Cio arylcarbonyloxy(C 1 -C 4 alkoxy)carbonyl, C 4 -C 11 cycloalkylcarbonyloxy(Ci-C 4 alkoxy) carbonyl; R 2a i s R 2 or R ( R 3) N ( R 2 N= ) C . U is selected from: a single bond, - (C 1 -C 7 alkyl) -, - (C 2 -C 7 alkenyl) - , - (C 2 -C 7 alkynyl) -, -(aryl)- substituted with 0-3 R 6a , or - (pyridyl) - substituted with 0-3 R 6a ; V is selected from: a single bond; - (C 1 -C 7 alkyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; - (C 2 -C 7 alkenyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; - (C 2 -C 7 alkynyl)-, substituted with 0-3 groups independently selected from R 6 or R 7 ; -(phenyl)-, substituted with 0-2 groups independently selected from R 6 or R 7 ; -(pyridyl)-, substituted with 0-2 groups independently selected from R 6 or R 7 ; or -(pyridazinyl)-, substituted with 0-2 groups independently selected from R 6 or R 7 ,• W X is selected from: a single bond, - (C(R 4 ) 2 ) n -C(R 4 ) (R 8 ) -C(R 4 ) (R 4a ) -, with the proviso that when n is 0 or 1, then at least one of R 4a or R 8 is other than H or methyl; Y selected from: hydroxy, Ci to Cio alkyloxy, C 3 to Cn cycloalkyloxy, Cg to Cio aryloxy, C 7 to Cn aralkyloxy, C 3 to Cio alkylcarbonyloxyalkyloxy, C 3 to Cio alkoxycarbonyloxyalkyloxy, C 2 to Cio alkoxycarbonylalkyloxy, C 5 to Cio cycloalkylcarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonyloxyalkyloxy, C 5 to Cio cycloalkoxycarbonylalkyloxy, C 7 to Cn aryloxycarbonylalkyloxy, Cβ to Cι 2 aryloxycarbonyloxyalkyloxy, Cβ to Cι 2 arylcarbonyloxyaIkyloxy, C 5 to Cio alkoxyalkylcarbonyloxyalkyloxy, C 5 to Cio (5-alkyl-l,3-dioxa-cyclopenten-2-one- yDmethyloxy, Cio to C 14 (5-aryl-l, 3-dioxa-cyclopenten-2-one- yDmethyloxy, (R 2 ) (R 3 )N- (C 1 -C 10 alkoxy)-; Z 1 is -C-, -0-, or -NR 22 -; Z 2 is -0-, or -NR 22 -; R 4 is selected from H, C 1 -C 10 alkyl, C 1 -C 10 alkylcarbonyl, aryl, arylalkylene cycloalkyl, or cycloalkylalkylene; alternately, two R 4 groups on adjacent carbon atoms may join to form a bond, thereby to form a carbon- carbon double or triple bond between such adjacent carbon atoms; R 4a is selected from H, hydroxy, C 1 -C 10 alkoxy, nitro, N(R 5 )R 5a , -N(R 12 )R 13 , -N(R 16 )R 17 , C 1 -C 10 alkyl substituted with 0-3 R 6 , aryl substituted with 0-3 R 6 , or C 1 -C 10 alkylcarbonyl; R b is selected from H, Ci-Cg alkyl, C 2 -Cg alkenyl, C 2 -Cg alkynyl, hydroxy, Ci-Cg alkoxy, Ci-Cg alkylthio, Ci-Cg alkylsulfinyl, Ci-Cg alkylsulfonyl, nitro, Ci-Cg alkylcarbonyl, Cg-Cio aryl, -N(R 12 )R 13 ; halo, CF 37 CN, Ci-Cg alkoxycarbonyl, carboxy, piperidinyl, or pyridyl; R 5 is selected from H, Ci-Cβ alkyl, C -C alkenyl, C 3 -C11 cycloalkyl, C 4 -C 11 cycloalkylmethyl, Cg-Cio aryl, C 7 -C 11 arylalkyl, or C 1 -C 10 alkyl substituted with 0-2 R 4b ; R 5a is selected from hydrogen, hydroxy, Ci to CQ alkyl, C 2 to Cg alkenyl, C 3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl, Ci-Cg alkoxy, benzyloxy, Cg to Cio aryl, heteroaryl, C 7 to Cn arylalkyl, or C 1 -C 10 alkyl substituted with 0-2 R 4b ; alternately, R 5 and R 5a when both are substituents on the same nitrogen atom (as in -NR 5 R 5a ) can be taken together with the nitrogen atom to which they are attached to form 3-azabicyclononyl, 1,2,3,4- tetrahydro-1-quinolinyl, 1,2,3,4-tetrahydro-2- isoquinolinyl, 1-piperidinyl, 1-morpholinyl, 1- pyrrolidinyl, thiamorpholinyl, thiazolidinyl or 1- piperazinyl, each being optionally substituted with Ci-Cg alkyl, Cg-Cio aryl, heteroaryl, C 7 -Cn arylalkyl, Ci-Cg alkylcarbonyl, C 3 -C 7 cycloalkylcarbonyl, Ci-C alkoxycarbonyl, C 7 -C 11 arylalkoxycarbonyl, Ci-Cg alkylsulfonyl or Cg-Cio arylsulfonyl; R 5b is selected from Ci-Cs alkyl, C 2 _ C alkenyl, C 3 -C 11 cycloalkyl, C 4 -C 11 cycloalkylmethyl, Cg-Cio aryl, C -C ϋ arylalkyl, or C 1 -C 10 alkyl substituted with 0-2 R b ; R 6 is selected from H, C 1 -C 10 alkyl, hydroxy, C 1 -C1 0 alkoxy, nitro, C 1 -C 10 alkylcarbonyl, -N(R 12 )R 13 , cyano, halo, CF 3 , CH0, C0 2 R 5 , C(=0)R 5a , C0NR 5 R 5a , 0C(=0)R 5a , 0C(=0)0R 5b , OR 5 , OC (=0) NR 5 R 5a , 0CH 2 C0 2 R 5 , C0 2 CH 2 C0 2 R 5 , N0 2 , NR 5a C(=0)R 5a , NR 5a C(=0) 0R 5 , NR 5a C(=0)NR 5 R 5a , NR 5a S0 2 NR 5 R 5a , NR 5a S0 2 R 5 , S(0) p R 5 , Sθ2NR 5 R 5a , C2 to Cg alkenyl, C3 to Cn cycloalkyl, C4 to Cn cycloalkylmethyl; Cg to Cio aryl optionally substituted with 1-3 groups selected from halogen, Ci-Cg alkoxy, Ci-Cg alkyl, CF 3 , S(0)mMe, or -NMe 2 ; C7 to Cn arylalkyl, said aryl being optionally substituted with 1-3 groups selected from halogen, Ci-C alkoxy, Ci-Cg alkyl, CF 3 , S(0)mMe, or -NMe 2 ; methylenedioxy when R 6 is a substiuent on aryl; or a 5-6 membered heterocyclic ring containing 1-2 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R 7 ; R 6a is selected from C1-C 4 alkyl, C1-C4 alkoxy, halo, CF 3 , N0 , or NR 1 R 13 ; R 7 is selected from H, C1-C10 alkyl, hydroxy, C1-C10 alkoxy, nitro, C1-C10 alkylcarbonyl, -N(R 1 )R 13 , cyano, halo, CF 3 , CHO, C0 2 R 5 , C(=0)R 5a , C0NR 5 R 5a , 0C(=0)R 5a , 0C(=0)0R 5b , OR 5a , OC(=0) NR 5 R 5a , 0CH 2 C0 2 R 5 , C0 2 CH C0 2 R 5 , N0 2 , NR 5a C(=0)R 5a , NR 5a C (=0) 0R 5b , NR Sa C(=0)NR 5 R 5a , NR 5a S0 2 NR 5 R 5a , NR 5a S0 2 R 5 , S(0) m R 5a , S0 2 NR 5 R 5a , C 2 to Cg alkenyl, C3 to Cn cycloalkyl, C 4 to Cn cycloalkylmethyl, Cg to Cio aryl, or C 7 to Cn arylalkyl; R 8 is selected from: R 6 ; C 2 -Cιo alkyl, substituted with 0-3 R 6 ; -Cιo alkenyl, substituted with 0-3 R 6 ; 2 _ o alkynyl, substituted with 0-3 R 6 ; 3 -C 8 cycloalkyl, substituted with 0-3 R 6 ; Cs-C cycloalkenyl, substituted with 0-3 R 6 ; aryl, substituted with 0-3 R 6 ; 5-6 membered heterocyclic ring containing 1-2 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R 6 ; R 12 and R 13 are independently H, C 1 -C 10 alkyl, Cι-Cι 0 alkoxycarbonyl, C 1 -C 10 alkylcarbonyl, Cι-Cι 0 alkylsulfonyl, aryl(Cι-Cιo alkyl) sulfonyl, arylsulfonyl, aryl, C 2 -Cg alkenyl, C 3 -C 11 cycloalkyl, C 4 -C u cycloalkylalkyl, C 7 -C n ary l a lk y l , C 7 -C 11 arylcarbonyl, C 4 -C 11 cycloalkoxycarbonyl, C 7 - Cn bicycloalkoxycarbonyl, C 7 -Cn aryloxycarbonyl, or aryl(Cι-Cιo alkoxy) carbonyl, wherein said aryls are optionally substituted with 0-3 substituents selected from the group consisting of: C 1 -C 4 alkyl, C 1 -C alkoxy, halo, CF 3 , and N0 2 ; R 14 is selected from H, C 1 -C 10 alkyl, C 2 -Cιo alkenyl, C -Cιo alkynyl, C 1 -C 10 alkoxy, aryl, heteroaryl or C 1 -C 10 alkoxycarbonyl, C0 2 R 5 or -C(=0)N(R 5 )R 5a ; R 15 is selected from: H; R 6 ; C 1 -C 10 alkyl, substituted with 0-3 R 6 ; C 2 -Cιo alkenyl, substituted with 0-3 R 6 ; Ci-Cio alkoxy, substituted with 0-3 R 6 ; aryl, substituted with 0-3 R 6 ; 5-6 membered heterocyclic ring containing 1-2 N, 0, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R 6 ; Ci-Cio alkoxycarbonyl substituted with 0-2 R 6 ; -C0 2 R 5 ; or -C(=0)N(R 12 )R 13 ; provided that when b is a double bond, only one of R 14 or R 15 is present; R 16 is selected from: -C(=0) -0-R 18a , -C(=0) -R 18b , -C(=0)N(R 18b ) 2 , -C(=0)NHS0 2 R 18a , -C(=0)NHC(=0)R 18b , -C(=0)NHC(=0)OR 18a , - C (=0) NHS0 NHR 18b , -C(=S) -NH-R 18b , -NH-C(=0) -0-R 18a , -NH-C(=0) -R 18b , -NH-C(=0) -NH-R 18b , -S0 2 -0-R 18a , -S0 2 -R 18a , -S0 2 -N(18 b ) 2 , -S0 2 -NHC(=0)018 b , -P(=S) (OR 18a ) 2 , -P(=0) (OR 18a ) 2 , -P(=S) (R 18a ) 2 , -P(=0) (R 18a ) 2 , or R 17 is selected from: H, Ci-Cio alkyl, C 2 -Cg alkenyl, C 3 - Cn cycloalkyl, C 4 -C 15 cycloalkylalkyl, aryl, aryl (C x -Ci 0 alkyl) - ; R i8a j_ s selected from: Ci-Cβ alkyl substituted with 0-2 R 19 , C 2 -Cβ alkenyl substituted with 0-2 R 19 , C -Cβ alkynyl substituted with 0-2 R 19 , 3 -C 8 cycloalkyl substituted with 0-2 R 19 , aryl substituted with 0-4 R 19 , aryl(Cι-Cg alkyl)- substituted with 0-4 R 19 , a 5-10 membered heterocyclic ring system having 1-3 heteroatoms selected independently from 0, S, and N, said heterocyclic ring being substituted with 0-4 R 19 , Ci-Cg alkyl substituted with a 5-10 membered heterocyclic ring system having 1-3 heteroatoms selected independently from O, S, and N, said heterocyclic ring being substituted with 0-4 R 19 ; i 8b 2.s selected from R 18 or H; R 19 is selected from H, halogen, CF 3 , CN, N0 2 , NR 12 R 13 , Ci-Cβ alkyl, C 2 -C 6 alkenyl, C 2 -Cg alkynyl, C 3 -Cn cycloalkyl, C 4 -C 11 cycloalkylalkyl, aryl, aryl(Cι-Cg alkyl)-, Ci-C alkoxy, or C 1 -C 4 alkoxycarbonyl; R 20 and R 21 are each independently selected from H, C 1 -C 10 alkyl, C0 2 R 5 , C(=0)R 5a , CONR 5 R 5a , NR 5 C(=0)R 5a , NR 12 R 13 , C 2 -C 6 alkenyl, C 3 -C u cycloalkyl, C 4 -Cn cycloalkylmethyl, Cg-Cio aryl, or C 7 -Cn arylalkyl; R 22 is selected from Ci-Cio alkyl, C 2 -Cg alkenyl, C 3 -C 1 1 cycloalkyl, C 4 -C 15 cycloalkylalkyl, aryl, aryKCi- C 10 alkyl)-; C(=0)R 5a , C0 2 R 5b , -C(=0)N(R 5 )R 5a , or a bond to X; m is 0-2 n is 0-2 p is 1-2 q is 1-7 r is 0-3 provided that n, q and r are chosen such that the number of atoms connecting R 1 and Y is in the range of 8-17. 25. A compound of Claim 24 of Formula Ic: (IC) wherein: Z is selected from a bond, O, or S; R 2 is selected from H, aryl(Cι-Cιo alkoxy)carbonyl, or C 1 -C 10 alkoxycarbonyl; U is a single bond; X is -CHR 4a -; R 5 is selected from H or C 1 -C 10 alkyl substituted with 0 - 6 R 4b ; R 6 and R 7 are each independently selected from H, Ci-Cio alkyl, hydroxy, Ci-Cio alkoxy, nitro, Ci-Cio alkylcarbonyl, -N(R 12 )R 13 , cyano, or halo; R 12 and R 13 are each independently selected from H, Ci-Cio alkyl, Ci-Cio alkoxycarbonyl, Ci-Cio alkylcarbonyl, Ci-Cio alkylsulfonyl, aryl(Cι-Cιo alkyl) sulfonyl, arylsulfonyl, or aryl, wherein said aryls are optionally substituted with 0-3 substituents selected from the group consisting of: C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halo, CF 3 , and N0 2 ; R 15 is selected from H, C 1 -C 10 alkyl, C 2 -Cιo alkenyl, C 2 'Cιo alkynyl, C 1 -C 10 alkoxy, aryl, heteroaryl or C -C 10 alkoxycarbonyl, C0 R 5 or -C(=0)N(R 5 )R 5a ; R 16 is selected from: -C(=0) -0-R 18a , -C(=0) -R l8 , -S(=0) 2 -R 18a ; R 17 is selected from: H or C 1 -C 4 alkyl; R i8a i s selected from: Ci-Cβ alkyl substituted with 0-2 R 19 , C 2 -Cβ alkenyl substituted with 0-2 R 19 , C 2 -Cβ alkynyl substituted with 0-2 R 19 , C 3 -C 8 cycloalkyl substituted with 0-2 R 19 , aryl substituted with 0-2 R 19 , aryl(Cι-Cg alkyl)- substituted with 0-2 R 19 , a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, triazolyl, imidazolyl, benzofuranyl, indolyl, indolinyl, quinolinyl, isoquinolinyl, isoxazolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyridinyl, 3H-indolyl, carbazolyl, pyrrolidinyl, piperidinyl, indolinyl, or morpholinyl, said heterocyclic ring being substituted with 0-2 R 19 ; Ci-Cg alkyl substituted with a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolinyl, benzofuranyl, indolyl, indolenyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyridinyl, 3H-indolyl, indolyl, carbazole, pyrrolidinyl, piperidinyl, indolinyl, or morpholinyl, said heterocyclic ring being substituted with 0-2 R 19 . 26. A compound of Claim 24 of Formula lb: (lb) wherein: R 1 is selected from: R 2 <R 3 )N-, R NH(R 2 N=) C- , R 2 R 3 N(CH 2 )p»Z-, R 2 NH(R 2 N=)CNH(CH 2 ) P -Z-, n is 0-1; p 1 is 2-4; p" is 4 - 6 ; Z is selected from a bond or 0; R 3 is H or C 1 - C 5 alkyl ; V is a single bond, or - (phenyl) -; X is selected from: -CH 2 -, -CHN(R 16 )R 17 -, or -CHNR 5 R 5a -; Y is selected from: hydroxy; Ci to Cio alkoxy; methylcarbonyloxymethoxy- ; ethylcarbonyloxymethoxy-; t-butylcarbonyloxymethoxy- ; cyclohexylcarbonyloxymethoxy- ; 1- (methylcarbonyloxy)ethoxy- ; 1- (ethylcarbonyloxy) ethoxy- ; 1- (t-butylcarbonyloxy)ethoxy- ; 1- (cyclohexylcarbonyloxy) ethoxy- ; i-propyloxycarbonyloxymethoxy-; t-butyloxycarbonyloxymethoxy- ; 1- (i-propyloxycarbonyloxy)ethoxy-; 1- (cyclohexyloxycarbonyloxy)ethoxy- ; 1- (t-butyloxycarbonyloxy) ethoxy- ; dimethylaminoethoxy- ; diethylaminoethoxy- ; (5-methyl-1,3-dioxacyclopenten-2-on-4-yl)methoxy- ; (5- (t-butyl) -1, 3-dioxacyclopenten-2-on-4- y1)methoxy- ; (1,3-dioxa-5-phenyl-eyelopenten-2-on-4-yl)methoxy- ; 1- (2- (2-methoxypropyl) carbonyloxy)ethoxy- ; R ι β a -i_ s selected from: C 1 -C 4 alkyl substituted with 0-2 R 19 , C -C 4 alkenyl substituted with 0-2 R 19 , C 2 -C 4 alkynyl substituted with 0-2 R 19 , C 3 -C 4 cycloalkyl substituted with 0-2 R 19 , aryl substituted with 0-2 R 19 , aryl(Cι-C 4 alkyl)- substituted with 0-2 R 19 , a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, triazolyl, imidazolyl, benzofuranyl, indolyl, indolinyl, quinolinyl, isoquinolinyl, isoxazolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyridinyl, 3H-indolyl, carbazolyl, pyrrolidinyl, piperidinyl, indolinyl, or morpholinyl, said heterocyclic ring being substituted with 0-2 R 19 ; Ci-Cg alkyl substituted with a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolinyl, benzofuranyl, indolyl, indolenyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyridinyl, 3H-indolyl, indolyl, carbazole, pyrrolidinyl, piperidinyl, indolinyl, or morpholinyl, said heterocyclic ring being substituted with 0-2 R 19 . 27. A compound of Claim 26 wherein: R 1 is R 2 NH(R 2 N=)C- or R 2 NH(R 2 N=)CNH- and V is phenyl or pyridyl; or R 1 is , and V is a single bond; n is 1-2; R 3 is H or C 1 -C 5 alkyl; X is selected from: -CH 2 -, -CHN(R 16 )R 17 -, or -CHNR 5 R 5 -; W is selected from: m is 1-3; Y is selected from: hydroxy; θ U Ci to Cio alkoxy; methylcarbonyloxymethoxy- ; ethylcarbonyloxymethoxy- ; t-butylcarbonyloxymethoxy- ; cyclohexylcarbonyloxymethoxy- ; 1- (methylcarbonyloxy) ethoxy- ; 1- (ethylcarbonyloxy) ethoxy- ; 1- (t-butylcarbonyloxy) ethoxy- ; 1- (cyclohexylcarbonyloxy) ethoxy- ; i-propyloxycarbonyloxymethoxy- ; t-butyloxycarbonyloxymethoxy- ; 1- (i-propyloxycarbonyloxy)ethoxy- ; 1- (cyclohexyloxycarbonyloxy) ethoxy- ; 1- ( -butyloxycarbonyloxy) ethoxy- ; dimethylaminoethoxy- ; diethylaminoethoxy- ; (5-methyl-1,3-dioxacyclopenten-2-on-4-yl)methoxy- ; (5- ( -butyl) -1,3-dioxacyclopenten-2-on-4- yl)methoxy- ; (1,3-dioxa-5-phenyl-cyclopenten-2-on-4-yl)methoxy- ; 1- (2- (2-methoxypropyl) carbonyloxy) ethoxy- ; R 19 is H, halogen, C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, cyclopropylmethyl, aryl, or benzyl; R 20 and R 21 are both H; R 22 is H, C 1 -C 4 alkyl or benzyl. 28. A compond of Claim 24, or a pharmaceutically acceptable salt form thereof, selected from: 2- (R,S) -2-carboxymethyl-1- {5- (R,S) -N- [3- (4- amidinophenyl) isoxazolin-5-yl acetyl]piperidine; 2- (R,S) -2-carboxymethyl-1- {5- (R,S) -N- [3- (4- amidinophenyl) isoxazolin-5-yl acetyl] azepine; 2- (R, S) -2-carboxymethyl-1- {5- (R,S) -N- [3- (4- amidinophenyl) isoxazolin-5-yl acetyl]pyrrolidine; 3- (R, S) -carboxymethyl-4- {5- (R,S) -N- [3- (4- amidinophenyl) isoxazolin-5-yl acetyl]piperazine-2- one; 6- (R,S) -carboxymethyl-1- {5- (R,S) -N- [3- (4- amidinophenyl) isoxazolin-5-yl acetyl]piperidine-2- one; 5- (R, S) -carboxymethyl-1- {5- (R,S) -N- [3- (4- amidinophenyl) isoxazolin-5-yl acetyl]pyrrolidine-2- one; 7- (R,S) -carboxymethyl-1- {5- (R,S) -N- [3- (4- amidinophenyl)isoxazolin-5-yl acetyl]azetidine-2- one; 2- (R,S) -carboxymethyl-1- {5- (R,S) -N- [3- (4- amidinophenyl) isoxazolin-5-yl acetyl]pyrazolidine; 3- (R, S) -carboxymethyl-4- {5- (R,S) -N- [3- (4- amidinophenyl) isoxazolin-5-yl acetyl]morpholine. 29. A method for the prevention or treatment of thrombosis which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound of Claim 1, 6, 11, 16, 20, or 24. 30. A pharmaceutical composition comprising a therapeutically effective amount of a compound of Claim 1, 6, 11, 16, 20, or 24 and a pharmaceutically acceptable carrier. 31. A method of inhibiting the aggregation of blood platelets which comprises administering to a host in need of such inhibition a therapeutically effective amount of a compound of Claim 1, 6, 11, 16, 20, or 24 . 32. A method of treating thromboembolic disorders selected from thrombus or embolus formation, harmful platelet aggregation, reocclusion following thrombolysis, reperfusion injury, restenosis, atherosclerosis, stroke, myocardial infarction, and unstable angina, which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound of Claim 6. 33. A method for the treatment of thrombosis which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound of Claim 6 in combination with one or more additional therapeutic agents selected from: a thrombolytic agent, an anti-coagulant agent, or an anti-platelet agent. 34. A method of treating rheumatoid arthritis, asthma, allergies, adult respiratory syndrome, organ transplantation rejection, septic shock, psoriasis, contact dermatitis, osteoporosis, osteoarthritis, tumor metastasis, diabetic retinopathy, inflammatory conditions and inflammatory bowel disease, comprising administering to a host in need of such treatment a therapeutically effective amount of a compound of Claim 6.

Inventors: CAIN GARY AVONN, DEGRADO WILLIAM FRANK, OLSON RICHARD ERIC, SIELECKI-DZURDZ THAIS MOTRIA, WITYAK JOHN, XUE CHU-BIAO, CAIN, GARY, AVONN, DEGRADO, WILLIAM, FRANK, OLSON, RICHARD, ERIC, SIELECKI-DZURDZ, THAIS, MOTRIA, WITYAK, JOHN, XUE, CHU-BIAO
Applicants: DU PONT MERCK PHARMA, THE DU PONT MERCK PHARMACEUTICAL COMPANY
Application year: 1994
Main classification: C07D261
IPC codes: A61K31, A61P7, A61P9, A61P27, A61P29, A61P35, A61P37, A61P43, C07D261, C07D413, C07D417, C07D498, C07F7, C07F9